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. 2016 Nov 15;7:540. doi: 10.3389/fphys.2016.00540

Table 2.

Growth factors in response to mechanical or physical stress on different tissues.

Growth factor Native cells Experimental condition (expansion or stress) Effect on growth factor Major observations References
Epidermal growth factor (EGF) Macrophages, Fibroblasts Burn injuries Keratinocyte proliferation and migration Grayson et al., 1993
2 mm incisional wounds on the PU.1 null mouse Reepithelialisation Martin et al., 2003
Heparin-binding epidermal growth factor (HB-EGF) Macrophages Keratinocyte-specific HB-EGF-deficient mice Wound closure was markedly impaired Shirakata et al., 2005
Cells treated with tetracycline (TET) ↑↑ Overexpression of HB-EGF inhibits proliferation Stoll et al., 2012
Fibroblast growth factor 1, 2, and 4 (FGF 1, 2, and 4) Fibroblasts, Macrophages, Endothelial cells, Smooth muscle cells, Chondrocytes, Mast cells Cultured fibroblasts stimulated with IL-1α Fibroblast proliferation Angiogenesis Maas-Szabowski and Fusenig, 1996
Transforming growth factor-α (TGF-α) Macrophages, Keratinocytes Macrophages isolated from a wound site Keratinocyte migration and reepithelialisation Rappolee et al., 1988
Transforming growth factor-β1-3 (TGF-β1-3) Macrophages, Fibroblasts, Keratinocytes, Neutrophils Adult and fetal wounds II
Reepithelialisation of skin Epidermal differentiation Cowin et al., 2001a
Fetal and adult sheep incisional skin wounding TGF-β3 is anti-scarring Scheid et al., 2002
Amphiregulin (AR) Keratinocytes Serum free cultured human keratinocytes Keratinocyte proliferation Piepkorn et al., 1994
Keratinocyte growth factor (KGF or FGF7) Fibroblasts Wounded mice skin Delayed re-epithelialization due to reduced proliferation rate of epidermal keratinocytes Werner et al., 1994
Platelet derived growth factor (PDGF) Macrophages, Endothelial cells Acute incisional wounds in an aging mouse colony The low levels of PDGF in the old cause initial delay in fibroblasts and inflammatory cell infiltration and proliferation within the wounds Ashcroft et al., 1997
Hepatocyte growth factor (HGF) Mesenchymal cells, Hepatocytes, Adipocytes, Keratinocytes Adult rat excisional wounds Keratinocyte migration, and proliferation Angiogenesis Cowin et al., 2001b
Vascular endothelial growth factor (VEGF) Neutrophils, Macrophages, Endothelial cells, Fibroblasts, Immobilized VEGF in porous collagen scaffold Endothelial cell proliferation, migration, and angiogenesis Shen et al., 2008
Connective tissue growth factor (CTGF) Fibroblasts, Endothelia Scratched human corneal epithelial cells CTGF is strongly induced and caused pathophysiology in tissues by inducing matrix deposition, conversion of fibroblasts into contractile myofibroblasts Secker et al., 2008
Insulin-like growth factor-I (IGF-I) Fibroblasts, neutrophils, macrophages, hepatocytes and skeletal muscle Estrogen-deprived mice Keratinocyte and fibroblast proliferation and migration Collagen synthesis and re-epithelialization Emmerson et al., 2012
Rat surgical incision Re-epithelization Todorovic et al., 2008
Interleukin-I α and β (IL-I α and β) Neutrophils, Monocytes, Macrophages, Keratinocytes Irradiated fibroblasts Keratinocyte activation, migration and proliferation Induce KGF expression and fibroblasts creation Maas-Szabowski et al., 2000
Endothelin-I (ET-I) Keratinocytes, Fibroblasts, Endothelial cells Cyclic stretch of cultured rat aortic smooth muscle cells (raSMC) and porcine aortic endothelial cells (PAEC) ↑ (PAEC)
↓ (raSMC)
Reveal central role for the endothelin system in stretch-induced apoptosis of the smooth muscle cells. ET-1 binding to the ETB receptor subtype results in apoptosis rather than proliferation Cattaruzza et al., 2000, 2001.
Activin Keratinocytes, Fibroblasts, Inflammatory cells, Macrophages Normal and wounded skin Stimulates keratinocyte migration, fibroplasia, and matrix production Hübner et al., 1996

↑, increased in response to mechanical strain; ↓, decreased in response to mechanical strain; ↑↑, overexpression in response to mechanical strain; II, unchanged in response to mechanical strain.