Myo-REG

Relations list
Source	Effect	Target	Tissue	PMID
Activated FAP	transition	Activated FAP->Adipocyte	Skeletal muscle	23582327
FAPs, which do not arise from the myogenic lineage, are bipotential cells capable of giving rise to fibroblasts and adipocytes
Activated FAP	transition	Activated FAP->Fibroblast	Skeletal muscle	23582327
FAPs, which do not arise from the myogenic lineage, are bipotential cells capable of giving rise to fibroblasts and adipocytes
Activated FAP	transition	Activated FAP->Myoblast	Skeletal muscle	24682306
Collectively, these data support the conclusion that, in addition to the reported ability to support the myogenic potential of MuSCs, FAPs from young mdx mice show a “latent” myogenic phenotype that is derepressed by HDACis at the expense of their fibro-adipogenic potential.
Activated FAP	transition	Activated FAP->Osteocyte	Skeletal muscle	28842904
This multipotent progenitor population is distinct from satellite cells and is capable of fibroblastic, adipogenic, chondrogenic, and osteogenic differentiation
Activated FAP	secretes	COL1A1	Skeletal muscle	24232182
FAPs are major contributors to the deposition of several extracellular proteinsfor instance, certain collagen isoforms that are abundant in the supportive transitional ECM during muscle regeneration [65].
Activated FAP	secretes	COL3A1	Skeletal muscle	24232182
FAPs are major contributors to the deposition of several extracellular proteinsfor instance, certain collagen isoforms that are abundant in the supportive transitional ECM during muscle regeneration [65].
Activated FAP	secretes	FST	Skeletal muscle	23505062
ability to promote differentiation of adjacent satellite cells, through upregulation of the soluble factor follistatin.
Activated FAP	secretes	IL33	Skeletal muscle	28163303
This influence is further enhanced by the recruitment of Treg cells to regenerated muscle by IL-33 released by fibro-adipogenic progenitor -FAP- cells and possibly by macrophages.
Activated FAP	secretes	IL6	Skeletal muscle	20081841
This cell type also secretes high levels of IL-6, which promotes the differentiation of myogenic cells
Activated FAP	secretes	WISP	Skeletal muscle	30686765
Using transcriptomic profiling, we identify WNT1 Inducible Signaling Pathway Protein 1 (WISP1) as a FAP-derived matricellular signal that is lost during aging. WISP1 is required for efficient muscle regeneration and controls the expansion and asymmetric commitment of MuSCs through Akt signaling
Activated FAP->Adipocyte	transition	Adipocyte	Skeletal muscle	22307978
Intramuscular transplantation, together with clonal analysis in culture, revealed that these progenitors are multipotent, exhibiting the capacity for both BMP-dependent skeletogenic differentiation and spontaneous adipogenic differentiation
Activated FAP->Fibroblast	transition	Fibroblast	Skeletal muscle	22307978
colonies derived from single, FACS-sorted, progenitors exhibited both BMP2-dependent osteogenic differentiation and BMP2-independent adipogenic and smooth muscle/fibroblastic differentiation
Activated FAP->Myoblast	transition	Myoblast	Skeletal muscle	24682306
Collectively, these data support the conclusion that, in addition to the reported ability to support the myogenic potential of MuSCs, FAPs from young mdx mice show a “latent” myogenic phenotype that is derepressed by HDACis at the expense of their fibro-adipogenic potential.
Activated FAP->Osteocyte	transition	Osteocyte	Skeletal muscle	24232182
FAPs are mesenchymal stem cells resident in skeletal muscle that have the ability to differentiate into fibroblasts, adipocytes and possibly into bone and cartilage cells, although not into satellite cells or muscle fibres.
Activated satellite	transition	Activated satellite->Myoblast	Skeletal muscle	22493066
In mature resting muscles, satellite cells are predominantly quiescent. Upon muscle injury, satellite cells are activated, enter the cell cycle, and proliferate. The proliferating satellite cells, called myoblasts, subsequently withdraw from the cell cycle to either differentiate or self-renew
Activated satellite	secretes	FN1	Skeletal muscle	23290138
Taken together, these results demonstrate that cell-autonomous expression of FN by activated satellite cells within their niche is indispensable for the homeostatic regulation of the satellite cell pool size during regenerative myogenesis
Activated satellite->Myoblast	transition	Myoblast	Skeletal muscle	22493066
In mature resting muscles, satellite cells are predominantly quiescent. Upon muscle injury, satellite cells are activated, enter the cell cycle, and proliferate. The proliferating satellite cells, called myoblasts, subsequently withdraw from the cell cycle to either differentiate or self-renew
ANGPT1	stimulates	Quiescent satellite	Skeletal muscle	30016618
However, experiments suggested that pericytes specifically express Ang-1 and IGF-1 to regulate MuSC activation and myofiber hypertrophy, respectively
AREG	stimulates	Activated satellite->Myoblast	Skeletal muscle	28163303
AREG release by Treg cells increases the expression of myogenicregulatory factors that drive the later stages of muscle differentiation.
AREG	stimulates	M1 macrophage->M2 macrophage	Skeletal muscle	28163303
M1 macrophage populations then undergo a shift to a population that is biased towards the M2 pro-regenerative phenotype. Several ligands have important roles in promoting this phenotypic shift, including fibrinogen, amphiregulin -AREG- and interleukin-10 produced by regulatory T cells.
ARG1	stimulates	Fibroblast	Skeletal muscle	28163303
ARG1 has an important role in fibrosis via its metabolism of arginine to yield polyamines, which stimulate fibroblast proliferation
CCL2	stimulates	Monocyte	Skeletal muscle	24232182
Neutrophils promote the proinflammatory environment that is necessary for the clearance of cellular debris. Under certain conditions, this cell type has been suspected to transiently aggravate tissue damage. Neutrophils also secrete the chemokines MIP-1a, MCP-1 and others that favour the recruitment of monocytes
CCL2	stimulates	Neutrophil	Skeletal muscle	28163303
Resident macrophages (that express F4/80, LY6C and CD11b, but lack expression of CXC-chemokine receptor 1 (CXCR1)) promote this marked neutrophil influx by releasing the neutrophil chemoattractants CXC-chemokine ligand 1 (CXCL1) and CC-chemokine ligand 2 -CCL2-
CCL3	stimulates	Monocyte	Skeletal muscle	24232182
Neutrophils promote the proinflammatory environment that is necessary for the clearance of cellular debris. Under certain conditions, this cell type has been suspected to transiently aggravate tissue damage. Neutrophils also secrete the chemokines MIP-1a, MCP-1 and others that favour the recruitment of monocytes
COL1A1	stimulates	ECM	Skeletal muscle	22045730
Furthermore, both in vitro and in vivo experiments show that PDGFRa+ cells exclusively express fibrosis markers, such as collagen types I and III, and connective tissue growth factor
COL1A2	stimulates	ECM	Skeletal muscle	22045730
Furthermore, both in vitro and in vivo experiments show that PDGFRa+ cells exclusively express fibrosis markers, such as collagen types I and III, and connective tissue growth factor
COL6A1	stimulates	ECM	Skeletal muscle	24232182
Moreover, macrophages also secrete different ECM proteins according to the stage of macrophage differentiation. For example, M2 macrophages secrete a more mature form of fibronectin and a higher amount of ColVI than do M1 macrophages. The ECM proteins secreted by M2 macrophages are important components of the muscle stem cell niche and promote self-renewal of satellite cells
CXCL1	stimulates	Neutrophil	Skeletal muscle	20219869
Several observations support the possibility that CXCL1 or CXCL5 release from activated or mechanically perturbed muscles may contribute to activating the Th1 response to injured muscle and subsequent muscle regeneration. First, induction and release of the chemokines is rapid; both were present at elevated concentrations in the media of stimulated muscles within 3 h of stimulation (76). In addition, both chemokines are chemoattractant to neutrophils, which become significantly elevated in muscle within a few hours of injury, and they would be sufficient to drive further the Th1 inflammatory response
CXCL1	stimulates	Neutrophil	Skeletal muscle	28163303
Resident macrophages (that express F4/80, LY6C and CD11b, but lack expression of CXC-chemokine receptor 1 (CXCR1)) promote this marked neutrophil influx by releasing the neutrophil chemoattractants CXC-chemokine ligand 1 (CXCL1) and CC-chemokine ligand 2 -CCL2-
CXCL5	stimulates	Neutrophil	Skeletal muscle	20219869
Several observations support the possibility that CXCL1 or CXCL5 release from activated or mechanically perturbed muscles may contribute to activating the Th1 response to injured muscle and subsequent muscle regeneration. First, induction and release of the chemokines is rapid; both were present at elevated concentrations in the media of stimulated muscles within 3 h of stimulation (76). In addition, both chemokines are chemoattractant to neutrophils, which become significantly elevated in muscle within a few hours of injury, and they would be sufficient to drive further the Th1 inflammatory response
Damaged myofiber	secretes	CXCL1	Skeletal muscle	20219869
Several observations support the possibility that CXCL1 or CXCL5 release from activated or mechanically perturbed muscles may contribute to activating the Th1 response to injured muscle and subsequent muscle regeneration. First, induction and release of the chemokines is rapid; both were present at elevated concentrations in the media of stimulated muscles within 3 h of stimulation (76). In addition, both chemokines are chemoattractant to neutrophils, which become significantly elevated in muscle within a few hours of injury, and they would be sufficient to drive further the Th1 inflammatory response
Damaged myofiber	secretes	CXCL5	Skeletal muscle	20219869
Several observations support the possibility that CXCL1 or CXCL5 release from activated or mechanically perturbed muscles may contribute to activating the Th1 response to injured muscle and subsequent muscle regeneration. First, induction and release of the chemokines is rapid; both were present at elevated concentrations in the media of stimulated muscles within 3 h of stimulation (76). In addition, both chemokines are chemoattractant to neutrophils, which become significantly elevated in muscle within a few hours of injury, and they would be sufficient to drive further the Th1 inflammatory response
Damaged myofiber	attracts	Eosinophil	Skeletal muscle	24232182
Muscle damage results in rapid recruitment of eosinophils, which secrete IL-4 to activate the regenerative actions of muscle resident fibro/adipocyte progenitors (FAPs)
Damaged myofiber	attracts	Mast cell	Skeletal muscle	24232182
In resting conditions, adult skeletal muscle contains different types of resident leukocyte. The most abundant are mast cells and macrophages. These resident cell types, in conjunction with patrolling circulatory monocytes, act as sensors for distress and secrete a number of chemoattractive molecules following muscle injury. Particularly, damage-activated mast cells almost instantly begin to secrete TNF-a, histamine and tryptase and then initiate the de novo synthesis of other cytokines, such as interleukin-6
Damaged myofiber	attracts	Monocyte	Skeletal muscle	24232182
In resting conditions, adult skeletal muscle contains different types of resident leukocyte. The most abundant are mast cells and macro phages. These resident cell types, in conjunction with patrolling circulatory monocytes, act as sensors for distress and secrete a number of chemo attractive molecules following muscle injury. Beyond the first day after injury, monocytes gradually become the predominant leukocytes in the exudate.
Damaged myofiber	attracts	Treg	Skeletal muscle	27479876
New studies show that injured muscle is also infiltrated by a specialized population of regulatory T cells, which control both the inflammatory response, by promoting the M1-to-M2 switch, and the activation of satellite cell
ECM	stimulates	FGF2	Skeletal muscle	25047058
Heparan sulfate proteoglycans (HSPGs) interact with a large number of growth factors in the muscle BL including insulin-like growth factor (IGF), fibrobast growth factor (FGF), hepatocyte growth factor (HGF) and transforming growth factor beta (TGF-?), all known to influence SC proliferation and differentiation (53, 54). HSPGs can increase the local concentration of growth factors, or sequester them away from cells and even participate in their function by complexing with them, dramatically affecting the local environment and driving cell behavior.
ECM	stimulates	HGF	Skeletal muscle	25047058
Heparan sulfate proteoglycans (HSPGs) interact with a large number of growth factors in the muscle BL including insulin-like growth factor (IGF), fibrobast growth factor (FGF), hepatocyte growth factor (HGF) and transforming growth factor beta (TGF-?), all known to influence SC proliferation and differentiation (53, 54). HSPGs can increase the local concentration of growth factors, or sequester them away from cells and even participate in their function by complexing with them, dramatically affecting the local environment and driving cell behavior.
ECM	stimulates	IGF1	Skeletal muscle	25047058
Heparan sulfate proteoglycans (HSPGs) interact with a large number of growth factors in the muscle BL including insulin-like growth factor (IGF), fibrobast growth factor (FGF), hepatocyte growth factor (HGF) and transforming growth factor beta (TGF-?), all known to influence SC proliferation and differentiation (53, 54). HSPGs can increase the local concentration of growth factors, or sequester them away from cells and even participate in their function by complexing with them, dramatically affecting the local environment and driving cell behavior.
ECM	stimulates	Quiescent satellite	Skeletal muscle	12181355
HGF is a heparin-binding growth factor that has been localized in the extracellular domain of uninjured skeletal muscle fibers, and after injury HGF quickly associates with satellite cells. Furthermore, quiescent and activated satellite cells have been shown to express the c-met receptor, which mediates the intracellular signaling response of HGF, which is consistent with the proposed role of HGF in activating quiescent satellite cells
ECM	stimulates	TGFB1	Skeletal muscle	25047058
Heparan sulfate proteoglycans (HSPGs) interact with a large number of growth factors in the muscle BL including insulin-like growth factor (IGF), fibrobast growth factor (FGF), hepatocyte growth factor (HGF) and transforming growth factor beta (TGF-?), all known to influence SC proliferation and differentiation (53, 54). HSPGs can increase the local concentration of growth factors, or sequester them away from cells and even participate in their function by complexing with them, dramatically affecting the local environment and driving cell behavior.
Eosinophil	secretes	IL13	Skeletal muscle	24232182
Regulation of cellular crosstalk also involves eosinophils that are recruited during the early stages of regeneration [37]. Eosinophils release the cytokines IL-4 and IL-13, which induce the proliferation of FAPs and simultaneously block their adipogenic differentiation.
Eosinophil	secretes	IL4	Skeletal muscle	24232182
Regulation of cellular crosstalk also involves eosinophils that are recruited during the early stages of regeneration [37]. Eosinophils release the cytokines IL-4 and IL-13, which induce the proliferation of FAPs and simultaneously block their adipogenic differentiation.
Fibroblast	secretes	COL1A1	Skeletal muscle	22045730
During normal wound healing in adult animals, fibroblasts initially migrate into the wound area and, as they do so, lay down a collagen- and cellular fibronectin-rich ECM
Fibroblast	secretes	COL1A2	Skeletal muscle	22045730
During normal wound healing in adult animals, fibroblasts initially migrate into the wound area and, as they do so, lay down a collagen- and cellular fibronectin-rich ECM
Fibroblast	secretes	FN1	Skeletal muscle	24232182
Fibroblasts are heterogeneous,with expression profiles that differ depending on the tissue source. A major function of this cell type is the deposition of fibrillar ECM, such as collagen and fibronectin, and basement membrane constituents
Fibroblast	secretes	MSTN	Skeletal muscle	18453534
Myostatin expression in fibroblasts is not limited to muscle [...]. Myostatin produced from fibroblasts is biologically active.
FN1	stimulates	Activated satellite	Skeletal muscle	23290138
Taken together, these results demonstrate that cell-autonomous expression of FN by activated satellite cells within their niche is indispensable for the homeostatic regulation of the satellite cell pool size during regenerative myogenesis
FN1	stimulates	ECM	Skeletal muscle	24232182
Moreover, macrophages also secrete different ECM proteins according to the stage of macrophage differentiation. For example, M2 macrophages secrete a more mature form of fibronectin and a higher amount of ColVI than do M1 macrophages. The ECM proteins secreted by M2 macrophages are important components of the muscle stem cell niche and promote self-renewal of satellite cells
HGF	stimulates	Quiescent satellite	Skeletal muscle	12181355
HGF is a heparin-binding growth factor that has been localized in the extracellular domain of uninjured skeletal muscle fibers, and after injury HGF quickly associates with satellite cells. Furthermore, quiescent and activated satellite cells have been shown to express the c-met receptor, which mediates the intracellular signaling response of HGF, which is consistent with the proposed role of HGF in activating quiescent satellite cells
IFNG	stimulates	M1 macrophage	Skeletal muscle	28163303
Although phagocytic macrophages biased towards the M1 phenotype remove debris resulting from muscle injury, they also express IFN gamma, which may reinforce the macrophage phenotype and retain MPCs in a proliferative, non-differentiated state so that their populations can expand and support tissue repair
IFNG	stimulates	Quiescent satellite	Skeletal muscle	28163303
Although phagocytic macrophages biased towards the M1 phenotype remove debris resulting from muscle injury, they also express IFN gamma, which may reinforce the macrophage phenotype and retain MPCs in a proliferative, non-differentiated state so that their populations can expand and support tissue repair
IGF1	stimulates	Quiescent satellite	Skeletal muscle	30016618
However, experiments suggested that pericytes specifically express Ang-1 and IGF-1 to regulate MuSC activation and myofiber hypertrophy, respectively
IL10	stimulates	M1 macrophage->M2 macrophage	Skeletal muscle	28163303
M1 macrophage populations then undergo a shift to a population that is biased towards the M2 pro-regenerative phenotype. Several ligands have important roles in promoting this phenotypic shift, including fibrinogen, amphiregulin -AREG- and interleukin-10 produced by regulatory T cells.
IL13	stimulates	Quiescent FAP->Activated FAP	Skeletal muscle	24232182
Eosinophils release the cytokines IL-4 and IL-13, which induce the proliferation of FAPs and simultaneously block their adipogenic differentiation
IL1B	stimulates	Quiescent satellite->Activated satellite	Skeletal muscle	24232182
IL-1, IL-6 and TNF-a secreted by M1 macrophages are particularly important to induce proliferative effects on myogenic cells
IL33	stimulates	Treg	Skeletal muscle	28163303
This influence is further enhanced by the recruitment of Treg cells to regenerated muscle by IL-33 released by fibro-adipogenic progenitor -FAP- cells and possibly by macrophages.
IL4	inhibits	Activated FAP->Adipocyte	Skeletal muscle	23582327
Activation of IL-4/IL-13 signaling promotes proliferation of FAPs to support myogenesis while inhibiting their differentiation into adipocytes
IL4	stimulates	Activated satellite->Myoblast	Skeletal muscle	24232182
IL-1, IL-6 and TNF-a secreted by M1 macrophages are particularly important to induce proliferative effects on myogenic cells, whereas IL-4 and IGF-1 released by M2 macrophages promote their differentiation [43,52,53].
IL4	stimulates	Quiescent FAP->Activated FAP	Skeletal muscle	24232182
Eosinophils release the cytokines IL-4 and IL-13, which induce the proliferation of FAPs and simultaneously block their adipogenic differentiation
IL5	stimulates	Eosinophil	Skeletal muscle	17259966
The array of mediators released by human mast cells is enormous and explains how mast cells can be involved in so many different physiological and pathophysiological functions. Of particular relevance...cytokines, such as IL-3 -basophil recruitment and activation-, IL-5 -eosinophil recruitment and activation- and IL-13 -induction of IgE synthesis by B cells-
IL6	stimulates	Quiescent satellite->Activated satellite	Skeletal muscle	24232182
At low physiological concentrations, TNF-a, tryptase and IL-6 promote activation and proliferation of satellite cells [31-33].
IL6	stimulates	Quiescent satellite->Activated satellite	Skeletal muscle	24232182
IL-1, IL-6 and TNF-a secreted by M1 macrophages are particularly important to induce proliferative effects on myogenic cells
M0 macrophage->M1 macrophage	transition	M1 macrophage	Skeletal muscle	22378047
In response to various signals, macrophages may undergo classical M1 activation (stimulated by TLR ligands and IFN-) or alternative M2 activation (stimulated by IL-4/IL-13)
M0 macrophage->M2 macrophage	transition	M2 macrophage	Skeletal muscle	22378047
In response to various signals, macrophages may undergo classical M1 activation (stimulated by TLR ligands and IFN-) or alternative M2 activation (stimulated by IL-4/IL-13)
M1 macrophage	secretes	CCL2	Skeletal muscle	28163303
Resident macrophages (that express F4/80, LY6C and CD11b, but lack expression of CXC-chemokine receptor 1 (CXCR1)) promote this marked neutrophil influx by releasing the neutrophil chemoattractants CXC-chemokine ligand 1 (CXCL1) and CC-chemokine ligand 2 -CCL2-
M1 macrophage	secretes	CXCL1	Skeletal muscle	28163303
Resident macrophages (that express F4/80, LY6C and CD11b, but lack expression of CXC-chemokine receptor 1 (CXCR1)) promote this marked neutrophil influx by releasing the neutrophil chemoattractants CXC-chemokine ligand 1 (CXCL1) and CC-chemokine ligand 2 -CCL2-
M1 macrophage	secretes	IFNG	Skeletal muscle	28163303
Although phagocytic macrophages biased towards the M1 phenotype remove debris resulting from muscle injury, they also express IFN gamma, which may reinforce the macrophage phenotype and retain MPCs in a proliferative, non-differentiated state so that their populations can expand and support tissue repair
M1 macrophage	secretes	IL1B	Skeletal muscle	24232182
IL-1, IL-6 and TNF-a secreted by M1 macrophages are particularly important to induce proliferative effects on myogenic cells
M1 macrophage	secretes	IL6	Skeletal muscle	23169615
the proinflammatory cytokines IL-6 and IL-1 are mainly secreted by M1 MPs
M1 macrophage	secretes	IL6	Skeletal muscle	24232182
IL-1, IL-6 and TNF-a secreted by M1 macrophages are particularly important to induce proliferative effects on myogenic cells
M1 macrophage	transition	M1 macrophage->M2 macrophage	Skeletal muscle	17485518
injured skeletal muscle recruits MOs exhibiting inflammatory profiles that operate phagocytosis and rapidly convert to antiinflammatory MPs that stimulate myogenesis and fiber growth
M1 macrophage	secretes	nitric oxide	Skeletal muscle	20219869
Furthermore, The expression of iNOS by M1 macrophages enables them to induce further muscle damage through production of cytotoxic levels of NO
M1 macrophage	secretes	nitric oxide	Skeletal muscle	18996917
For example, macrophages that are driven in vitro to a pro-inflammatory, M1 phenotype lyse muscle cells through inducible nitric oxide synthase iNOS-mediated processes, and macrophages that express CD68, a marker of M1 macrophages, are the first to invade injured muscle following acute injury
M1 macrophage	secretes	TNF	Skeletal muscle	24232182
IL-1, IL-6 and TNF-a secreted by M1 macrophages are particularly important to induce proliferative effects on myogenic cells
M1 macrophage->M2 macrophage	transition	M2 macrophage	Skeletal muscle	17485518
injured skeletal muscle recruits MOs exhibiting inflammatory profiles that operate phagocytosis and rapidly convert to antiinflammatory MPs that stimulate myogenesis and fiber growth
M2 macrophage	secretes	ARG1	Skeletal muscle	28163303
M2a macrophages secrete IL-10, and express CD206 and arginase 1 -ARG1-.
M2 macrophage	secretes	COL6A1	Skeletal muscle	24232182
For example, M2 macrophages secrete a more mature form of fibronectin and a higher amount of ColVI than do M1 macrophages [54,55]. The ECM proteins secreted by M2 macrophages are important components of the muscle stem cell niche and promote self-renewal of satellite cells [56,57].
M2 macrophage	secretes	FN1	Skeletal muscle	24232182
For example, M2 macrophages secrete a more mature form of fibronectin and a higher amount of ColVI than do M1 macrophages [54,55]. The ECM proteins secreted by M2 macrophages are important components of the muscle stem cell niche and promote self-renewal of satellite cells [56,57].
M2 macrophage	secretes	IGF1	Skeletal muscle	20304951
Macrophages also release mitogenic growth factors for myogenic cells and establish cell-cell interactions that protect myogenic cells from apoptosis. IL-4, IL-6, fibroblast growth factor, and IGF-1 as well as several other cytokines and growth factors influence myogenic cell behavior
M2 macrophage	secretes	IL10	Skeletal muscle	28163303
M2a macrophages secrete IL-10, and express CD206 and arginase 1 -ARG1-.
M2 macrophage	secretes	IL33	Skeletal muscle	28163303
This influence is further enhanced by the recruitment of Treg cells to regenerated muscle by IL-33 released by fibro-adipogenic progenitor -FAP- cells and possibly by macrophages.
M2 macrophage	secretes	IL4	Skeletal muscle	20304951
Macrophages also release mitogenic growth factors for myogenic cells and establish cell-cell interactions that protect myogenic cells from apoptosis. IL-4, IL-6, fibroblast growth factor, and IGF-1 as well as several other cytokines and growth factors influence myogenic cell behavior
M2 macrophage	secretes	TGFB1	Skeletal muscle	28163303
FAP cell proliferation and differentiation into cells with phagocytic or fibrogenic phenotypes are influenced by the release of transforming growth factor-beta -TGF beta- from macrophages and by IL-4 released by eosinophils.
Mast cell	secretes	Histamine	Skeletal muscle	17259966
Mast cells... release histamine and other mediators after crosslinking of surface-bound IgE by allergen.
Mast cell	secretes	Histamine	Skeletal muscle	24232182
Particularly, damage-activated mast cells almost instantly begin to secrete TNFa, histamine and tryptase and then initiate the de novo synthesis of other cytokines, such as interleukin (IL)6
Mast cell	secretes	IL5	Skeletal muscle	17259966
The array of mediators released by human mast cells is enormous and explains how mast cells can be involved in so many different physiological and pathophysiological functions. Of particular relevance...cytokines, such as IL-3 -basophil recruitment and activation-, IL-5 -eosinophil recruitment and activation- and IL-13 -induction of IgE synthesis by B cells-
Mast cell	secretes	IL6	Skeletal muscle	24232182
Particularly, damage-activated mast cells almost instantly begin to secrete TNFa, histamine and tryptase and then initiate the de novo synthesis of other cytokines, such as interleukin (IL)6
Mast cell	secretes	Leukotriene B4	Skeletal muscle	17259966
The array of mediators released by human mast cells is enormous and explains how mast cells can be involved in so many different physiological and pathophysiological functions. Of particular relevance in the pathogenesis of allergic inflammation are...LTB4, which targets neutrophils and mast-cell progenitors
Mast cell	secretes	TNF	Skeletal muscle	24232182
Particularly, damage-activated mast cells almost instantly begin to secrete TNFa, histamine and tryptase and then initiate the de novo synthesis of other cytokines, such as interleukin (IL)6
Mast cell	secretes	TPSAB1	Skeletal muscle	24232182
Particularly, damage-activated mast cells almost instantly begin to secrete TNFa, histamine and tryptase and then initiate the de novo synthesis of other cytokines, such as interleukin (IL)6
Monocyte	secretes	IL1B	Skeletal muscle	24232182
Indeed, Ly6C+ monocytes promote the recruitment of other monocytes by secreting proinflammatory cytokines, such as TNF-a and IL-1
Monocyte	transition	M1 macrophage	Skeletal muscle	24232182
Once monocytes have invaded the tissue, they begin to differentiate into macrophages.
Monocyte	secretes	TNF	Skeletal muscle	24232182
Indeed, Ly6C+ monocytes promote the recruitment of other monocytes by secreting proinflammatory cytokines, such as TNF-a and IL-1
MPO	stimulates	Damaged myofiber	Skeletal muscle	20219869
LDL modification by MPO may be particularly important in regulating the process of tissue repair and regeneration in skeletal muscle; neutrophils that invade injured muscle in advance of M1 macrophages induce muscle membrane damage through the release of MPO. This may be one of several regulatory interactions that occur between neutrophils and macrophages during the early stage of muscle inflammation
MSTN	inhibits	Activated satellite->Myoblast	Skeletal muscle	12244043
Myostatin is an inhibitor of myoblast differentiation and that this inhibition is mediated through Smad 3.
Myoblast	secretes	DLL1	Skeletal muscle	17540178
Immunostaining of isolated myofibers revealed that Delta-1 was expressed at high levels in Pax7+/Myf5+ satellite cells but low levels in Pax7+/Myf5- cells
Myoblast	transition	Myocyte->Myofiber	Skeletal muscle	22147605
Upon myofiber culturing, the satellite cells proliferate, giving rise to satellite cell-derived myoblasts that can differentiate and form multinucleated myotubes
Myocyte->Myofiber	transition	Myofiber	Skeletal muscle	22147605
Upon myofiber culturing, the satellite cells proliferate, giving rise to satellite cell-derived myoblasts that can differentiate and form multinucleated myotubes
Myofiber	inhibits	Activated FAP->Adipocyte	Skeletal muscle	20081842
These results suggest that satellite cell-derived muscle fibres generate factors that strongly inhibit adipo- genic differentiation of PDGFRα+ cells.
Neutrophil	secretes	CCL2	Skeletal muscle	24232182
Neutrophils also secrete the chemokines MIP-1a, MCP-1 and others that favour the recruitment of monocytes
Neutrophil	secretes	CCL3	Skeletal muscle	24232182
Neutrophils also secrete the chemokines MIP-1a, MCP-1 and others that favour the recruitment of monocytes
Neutrophil	secretes	MPO	Skeletal muscle	20219869
LDL modification by MPO may be particularly important in regulating the process of tissue repair and regeneration in skeletal muscle; neutrophils that invade injured muscle in advance of M1 macrophages induce muscle membrane damage through the release of MPO. This may be one of several regulatory interactions that occur between neutrophils and macrophages during the early stage of muscle inflammation
Neutrophil	secretes	TNF	Skeletal muscle	25374568
Human and murine neutrophils also express and produce many TNF-superfamily members (Figure (Figure1A,B),1A,B), although at variable levels
nitric oxide	stimulates	Damaged myofiber	Skeletal muscle	20219869
Furthermore, The expression of iNOS by M1 macrophages enables them to induce further muscle damage through production of cytotoxic levels of NO
nitric oxide	stimulates	Damaged myofiber	Skeletal muscle	18996917
For example, macrophages that are driven in vitro to a pro-inflammatory, M1 phenotype lyse muscle cells through inducible nitric oxide synthase iNOS-mediated processes, and macrophages that express CD68, a marker of M1 macrophages, are the first to invade injured muscle following acute injury
Pericyte	secretes	ANGPT1	Skeletal muscle	30016618
However, experiments suggested that pericytes specifically express Ang-1 and IGF-1 to regulate MuSC activation and myofiber hypertrophy, respectively
Pericyte	secretes	IGF1	Skeletal muscle	30016618
However, experiments suggested that pericytes specifically express Ang-1 and IGF-1 to regulate MuSC activation and myofiber hypertrophy, respectively
Pericyte	transition	Myofiber	Skeletal muscle	21988915
Here we show that pericytes, transgenically labelled with an inducible Alkaline Phosphatase CreERT2, but not endothelial cells, fuse with developing myofibres and enter the satellite cell compartment during unperturbed postnatal development
Pericyte	transition	Pericyte->Adipocyte	Skeletal muscle	25278877
Skeletal muscle pericytes can differentiate in vitro toward adipogenic lineage (Farrington-Rock et al., 2004; Crisan et al., 2008a) but, like PDGFRα+ cells, do not generate myofibers, and only type-1 express PDGFRα. When purified type-1 pericytes are delivered intramuscularly in a mouse model of fatty infiltration, ectopic white fat is generated
Pericyte->Adipocyte	transition	Adipocyte	Skeletal muscle	25278877
Skeletal muscle pericytes can differentiate in vitro toward adipogenic lineage (Farrington-Rock et al., 2004; Crisan et al., 2008a) but, like PDGFRα+ cells, do not generate myofibers, and only type-1 express PDGFRα. When purified type-1 pericytes are delivered intramuscularly in a mouse model of fatty infiltration, ectopic white fat is generated
Quiescent FAP	transition	Quiescent FAP->Activated FAP	Skeletal muscle	20081841
These cells are quiescent in intact muscle but proliferate efficiently in response to damage. FAPs do not generate myofibres, but enhance the rate of differentiation of primary myogenic progenitors in co-cultivation experiments. In summary, FAPs expand upon damage to provide a transient source of pro-differentiation signals for proliferating myogenic progenitors
Quiescent FAP->Activated FAP	transition	Activated FAP	Skeletal muscle	20081841
These cells are quiescent in intact muscle but proliferate efficiently in response to damage. FAPs do not generate myofibres, but enhance the rate of differentiation of primary myogenic progenitors in co-cultivation experiments. In summary, FAPs expand upon damage to provide a transient source of pro-differentiation signals for proliferating myogenic progenitors
Quiescent satellite	transition	Quiescent satellite->Activated satellite	Skeletal muscle	22493066
In mature resting muscles, satellite cells are predominantly quiescent. Upon muscle injury, satellite cells are activated, enter the cell cycle, and proliferate
Quiescent satellite->Activated satellite	transition	Activated satellite	Skeletal muscle	22493066
In mature resting muscles, satellite cells are predominantly quiescent. Upon muscle injury, satellite cells are activated, enter the cell cycle, and proliferate
TGFB1	stimulates	Activated FAP->Fibroblast	Skeletal muscle	28163303
FAP cell proliferation and differentiation into cells with phagocytic or fibrogenic phenotypes are influenced by the release of transforming growth factor-beta -TGF beta- from macrophages and by IL-4 released by eosinophils.
TGFB1	stimulates	Activated FAP->Fibroblast	Skeletal muscle	26053624
Taken together, this confirms that in addition to regulating their survival, TGFB1 also induces the differentiation of FAPs along the fibrogenic lineage
TNF	induces apoptosis	Activated FAP	Skeletal muscle	26053624
In summary, our data show that inflammatory macrophages are both required for efficient FAP clearance by apoptosis in vivo and sufficient to induce their programmed cell death via a TNF-mediated mechanism in vitro. In addition, TNF-expressing macrophages are found in close proximity to FAPs during their clearance
TNF	induces apoptosis	Activated FAP	Skeletal muscle	28163303
FAP cells are then eliminated by apoptosis that is driven by TNF released from M1-biased macrophages
TNF	stimulates	M0 macrophage->M1 macrophage	Skeletal muscle	25339958
Albeit phagocytosis may provide the initial antigen stimulus, the activity of macrophages can be increased by cytokines secreted by helper T cells, with interferon gamma (IFN-) being one of the most potent macrophage activators
TNF	stimulates	Quiescent satellite->Activated satellite	Skeletal muscle	24232182
At low physiological concentrations, TNF-a, tryptase and IL-6 promote activation and proliferation of satellite cells [31-33].
TNF	stimulates	Quiescent satellite->Activated satellite	Skeletal muscle	24232182
IL-1, IL-6 and TNF-a secreted by M1 macrophages are particularly important to induce proliferative effects on myogenic cells
TPSAB1	stimulates	Myoblast	Skeletal muscle	21999702
Our data show that tryptase can stimulate myoblast proliferation and this effect is part of a signaling cascade dependent on PAR-2 activation and on the downstream activation of COX-2
TPSAB1	stimulates	Quiescent satellite	Skeletal muscle	23813613
Mast cells can also directly stimulate the proliferation of many cell types such as skeletal muscle, epithelial, and smooth muscle cells via tryptase, a serine protease only found in MCs and released after activation
TPSAB1	stimulates	Quiescent satellite->Activated satellite	Skeletal muscle	24232182
At low physiological concentrations, TNF-a, tryptase and IL-6 promote activation and proliferation of satellite cells [31-33].
Treg	secretes	AREG	Skeletal muscle	28163303
M1 macrophage populations then undergo a shift to a population that is biased towards the M2 pro-regenerative phenotype. Several ligands have important roles in promoting this phenotypic shift, including fibrinogen, amphiregulin -AREG- and interleukin-10 produced by regulatory T cells.
Treg	secretes	IL10	Skeletal muscle	28163303
M1 macrophage populations then undergo a shift to a population that is biased towards the M2 pro-regenerative phenotype. Several ligands have important roles in promoting this phenotypic shift, including fibrinogen, amphiregulin -AREG- and interleukin-10 produced by regulatory T cells.
WISP	stimulates	Activated satellite->Myoblast	Skeletal muscle	30686765
WISP1 is required for efficient muscle regeneration and controls the expansion and asymmetric commitment of MuSCs through Akt signaling

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Myogenesis and Muscle Regeneration Portal