Endostatin inhibits hypertrophic scarring in a rabbit ear model

Abstract

Abstract:Objective: The present study was designed to use an in vivo rabbit ear scar model to investigate the efficacy of systemic administration of endostatin in inhibiting scar formation. Methods: Eight male New Zealand white rabbits were randomly assigned to two groups. Scar model was established by making six full skin defect wounds in each ear. For the intervention group, intraperitoneal injection of endostatin was performed each day after the wound healed (about 15 d post wounding). For the control group, equal volume of saline was injected. Thickness of scars in each group was measured by sliding caliper and the scar microcirculatory perfusion was assessed by laser Doppler flowmetry on Days 15, 21, 28, and 35 post wounding. Rabbits were euthanatized and their scars were harvested for histological and proteomic analyses on Day 35 post wounding. Results: Macroscopically, scars of the control group were thicker than those of the intervention group. Significant differences between the two groups were observed on Days 21 and 35 (p<0.05). Scar thickness, measured by scar elevation index (SEI) at Day 35 post wounding, was significantly reduced in the intervention group (1.09±0.19) compared with the controls (1.36±0.28). Microvessel density (MVD) observed in the intervention group (1.73±0.94) was significantly lower than that of the control group (5.63±1.78) on Day 35. The distribution of collagen fibers in scars treated with endostatin was relatively regular, while collagen fibers in untreated controls were thicker and showed disordered alignment. Western blot analysis showed that the expressions of type I collagen and Bcl-2 were depressed by injection of endostatin. Conclusions: Our results from the rabbit ear hypertrophic scar model indicate that systemic application of endostatin could inhibit local hypertrophic scar formation, possibly through reducing scar vascularization and angiogenesis. Our results indicated that endostatin may promote the apoptosis of endothelial cells and block their release of platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF), thereby controlling collagen production by fibroblasts. Blood vessel-targeted treatment may be a promising strategy for scar therapy.

Endostatin inhibits fibrosis by modulating the PDGFR/ERK signal pathway: an in vitro study

“…Our previous study confirmed that systemic application of endostatin could prevent hypertrophic scar formation in the rabbit ear model (Ren et al, 2013). Yamaguchi et al (2012) found that endostatin-derived peptide ameliorates organ fibrosis that is triggered by transforming growth factor-β (TGF-β) and bleomycin in human and mouse tissues.…”

Recombinant Human Endostatin against the development of RIPF in a murine model

“…As previous studies showed that pretreatment of Endostatin could inhibit the fibrosis of human skin fibroblast and its transformation into MFBs [33]. Systemic administration of Endostatin could inhibit the rabbit ear local hypertrophic scar formation [34]. Parenteral or intratracheal administration of a peptide derived from Endostatin could prevent and ameliorate fibrosis in a bleomycin-induced pulmonary fibrosis model [35].…”

A Double-Blind, Randomized Trial Shows the Role of Zonal Priming and Direct Topical Application of Epigallocatechin-3-Gallate in the Modulation of Cutaneous Scarring in Human Skin

“…Because angiogenesis immediately precedes scar tissue formation in adult wounds, one study speculated that there was a coupled regulation (Wilgus et al, 2008). This notion has led to a number of trials evaluating antiangiogenic therapies to reduce skin scarring (Ren et al, 2013). High levels of angiogenesis have been identified in hypertrophic scars (Van der Veer et al, 2011) and keloid scars (Syed et al, 2013b), leading to suggestions that partial inhibition of the angiogenic response could reduce scar formation or the potential for development of abnormal skin scarring (Wietecha et al, 2015;Wilgus et al, 2008).…”