Table 1.

The role of growth factors in skeletal muscle regeneration

Growth factors	Physiological effects, potential benefits	Shortcomings	Commentary
IGF-1	- Essential for muscle growth during development and regeneration. - Promote myoblast proliferation and differentiation in vitro (Huard et al. 2002) - Hypertrophic effect of IGF-1 (Barton-Davis et al. 1999) - Serial injections of IGF-1 improve muscle healing in vivo (Menetrey et al. 2000). - Existence of a muscle specific isoform of IGF-1 (mIGF-1) (Musaro et al. 1999; Musaro et al. 2004)	- Chemotactic for fibroblasts, increase collagen production, enhance fibrosis development	- IGF-1 play a central role in the enhancement of muscle regeneration- - Anti-inflammatory actions of IGF-1 (Mourkioti and Rosenthal 2005; Tidball and Welc 2015)
HGF	- Promote myoblast proliferation and inhibit myoblast differentiation (Anderson 2016; Yin et al. 2013) - Important role for satellite cell activation. Balance between the activation of satellite cells and their return to quiescence. (Chazaud 2010) - Recently, it was shown that a second set of HGF production is crucial for inflammation resolution after injury (Proto et al. 2015)	- Injection of HGF into injured muscle increased myoblast numbers but blocked the regeneration process (Miller et al. 2000)	- HGF is important during the early phase of muscle regeneration, activate satellite cells
VEGF	- Important signaling protein that favor angiogenesis. - Promote myoblast migration, proliferation and survival. (Arsic et al. 2004) - VEGF administration improves muscle regeneration. (Messina et al. 2007; Deasy et al. 2009)	- Non regulated VEGF expression promote aberrant angiogenesis and fibrosis in skeletal muscle (Karvinen et al. 2011)	- Importance of the proximity between satellite cells and the microvasculature during muscle regeneration, role of VEGF
FGF	- Large family of mitogen involved in cell growth and survival - FGF-6 has a muscle specific expression, stimulates satellite cell proliferation and promotes myogenic terminal differentiation (Floss et al. 1997) - FGF-2 promote satellite cell proliferation and inhibit myogenic differentiation (Menetrey et al. 2000; Kastner et al. 2000)	- Stimulate fibroblast proliferation,	- FGF signaling plays a key role in muscle repair, blocking FGF signaling delay muscle regeneration (Saera-Vila et al. 2016).
TGF-β1	- Key regulator of the balance between muscle fibrosis and muscle regeneration - Inhibits satellite cell proliferation and differentiation in vitro	- Excessive TGFβ1-induced deposition of ECM at the site of injury, fibrosis (Garg et al. 2015).	- Anti fibrotic therapy by blocking overexpression of TGF-β1 improve muscle regeneration. (Burks et al. 2011; Hwang et al. 2016)
PDGF-BB	- PDGF isoforms can regulate myoblast proliferation and differentiation in vitro (Yablonka-Reuveni et al. 1990) - PDGF-BB stimulates satellite cell proliferation and inhibit their differentiation (Charge and Rudnicki 2004)	- Potent mitogen for fibroblasts	- Release from injured vessels and platelets, PDGF stimulates early skeletal muscle regeneration