Table 1.

Summary of growth factors present in the healing urethra.

Growth Factor	Evidence in Urethra and Wound Healing
Epidermal growth factor (EGF)	EGF receptor increases keratinocyte proliferation and cell migration leading to re-epithelialization in wound healing [11]. EGF is crucial for urethral and penile development, and is deficient in the skin adjacent to the urethra in boys with hypospadias, a congenital urethral defect [12,13,14]. The addition of EGF improves urothelial cell healing in an in vitro model of bladder injury repair [15].
Fibroblast growth factor-basic (FGF-basic)	FGF-basic (also known as FGF-2) also plays a role in wound healing by increasing granulation tissue formation, re-epithelialization, and tissue remodeling [11]. It is present in the developing urethra and required for proliferation of urethral progenitor cells of the epithelium [16].
Insulin-like growth factor-1 (IGF-1)	IGF-1 has been linked to wound healing by increasing keratinocyte motility and promotes a proliferative response in the wound [11]. The IGF-1 receptor is prominently found in the epithelium of the rat urethra [17]. IGF-1 has been shown to promote urothelial cell proliferation resulting in improved urethral wound healing via stricture prevention [18].
Platelet-derived growth factor (PDGF)	PDGF has a role in wound healing by increasing the expression of VEGF and IGF-1 to improve angiogenesis and re-epithelialization. PDGF also increases the proliferation and stimulation of fibroblasts [11]. Additionally, PDGF-BB has already been approved by the FDA for topical wound treatment in diabetic ulcers [19,20].
Transforming growth factor beta (TGF-β1)	TGF-β1 has been proven to promote acceleration of healing, and to have anti-scarring and anti-fibrotic effects [11,21]. The TGF- β1 receptor is found on the mouse genital tubercle during development, and receptor expression has decreased levels after urethral injury, so increased TGF-β1 may promote urethral healing [22,23].
Vascular endothelial growth factor (VEGF)	VEGF mediates angiogenesis by improving tissue ischemia and hypoxia, and limiting fibrosis and stricture [24]. VEGF receptor expression is decreased in urethral subepithelia; however, it has been shown that increased VEGF in urethral tissue supports urethral repair [22].