Platelet-derived growth factor induces fetal wound fibrosis

Regulation of scar formation by vascular endothelial growth factor

“…48,49 In addition, fetal studies have shown that factors capable of inducing angiogenesis, such as transforming growth factor-b (TGF-b), 50 platelet-derived growth factor, 51 basic fibroblast growth factor, 52 interleukin-8, 53 and prostaglandin E 2 , 54 are either present at lower levels during scarless healing or can induce scarring when added to these wounds. 10,48,[55][56][57] In line with these previous reports, our studies indicate that scarless fetal wounds heal without a robust increase in vascularity or VEGF levels, in contrast to fibrotic fetal wounds. Although several studies have suggested lower levels of angiogenesis in scarless fetal wounds, one recent study reported increased VEGF mRNA levels and angiogenesis in scarless compared to fibrotic fetal wounds.…”

Inhibition of Wound TGF Beta-1 by Celecoxib: A Possible Therapeutic Route for Scar Free Wound

“…This idea is in line with the fetal scarless healing characterised by a lack of inflammatory response and a lack of scar formation [19][20][21][22][23][24][25][26][27][28][29][30][31]. Interestingly, in this study we have shown macroscopic and microscopic reduction of post wounding inflammatory response and post wounding scarring simulating fetal wound without completely interfering with the inflammation.…”

“…TGF Beta-1 is secreted by dermal cells and by inflammatory cells infiltrating the wound; it promotes collagen deposition and remodelling [24][25][26]. Interestingly, exogenous application of TGF Beta-1 or PGE2 COX product to the fetal wound resulted in induction of inflammation and scar formation [27][28][29][30][31][32]. Therefore, the inflammatory mediators including COX product and TGF Beta-1 are determent factors affecting the postwounding scarring.…”

“…Previously we have studied several human disorders associated with abnormal wound healing such as chronic venous ulcers [49][50][51] diabetic ulcers [2,33] and keloids [34] and we have reported that the abnormality in healing was attributed primarily to the imbalance between endogenous mediators in the wound environment. Here we extended our study to an animal model of wound healing with interest in investigation of the postwounding scars and the role of COX-2 and TGF Beta-1, two mediators believed to have a crucial role in scar formation [24][25][26][27][28][29][30][31][32]. At time of injury or surgery, the main concern of both the patient and the surgeon is relieving inflammation and achieving wound closure, thus, NSAIDs are routinely used postoperative to achieve this shortterm target [52][53][54][55].…”

Looking proximally and distally: 100 years of limb regeneration and beyond

“…Skin regeneration in the mouse fetus is correlated with a minimal inflammatory response, reflected in lower numbers of platelets and macrophages, a lower ratio of TGF-b1, 2/TGF-b3, and type I/III collagens, lower levels of platelet-derived growth factor (PDGF) and its receptor, and higher levels of hyaluronic acid (HA) and its receptor (for review, see Stocum, 2006). Antibodies to TGF-b1, 2, or addition of exogenous TGF-b3 administered early in the course of adult mouse skin repair evoke a more regenerative response (Shah et al, 1994(Shah et al, , 1995, while hyaluronidase and PDGF administered to fetal skin shifts the wound response toward scarring (Haynes et al, 1994;Mast et al, 1995). Skin wounds in antibiotic-maintained PU.1 null mice, which lack macrophages and neutrophils, are repaired by regeneration (Martin et al, 2003).…”