title: Adenovirus-mediated METH1 gene expression inhibits hypertrophic scarring in a rabbit ear model.
abstract: Hypertrophic scarring remains a major problem for patients who have suffered from surgeries or burns. Vascularization plays an important role in the early phase of hypertrophic scarring. Therefore, the inhibition of angiogenesis might be used as a preventive strategy. In this study, we assessed the effect of anti-angiogenesis resulting from adenovirus-mediated METH1 (metalloprotease and thrombospondin1) gene expression on the hypertrophic scar formation in a rabbit ear model of hypertrophic scarring. We first investigated the number of microvessel and microcirculatory perfusion in untreated scars on days 10, 30, 60, and 90 after epithelialization. Then, we examined the effect of anti-angiogenesis by adenovirus-mediated METH1 expression on hypertrophic scar formation by calculating the scar elevation index, counting the microvessel and argyrophilic nucleolar organizer region particle, and detecting the amount of collagen on days 30 and 60 after treatment. We found that untreated scar tissues at the proliferative phase (days 10-60 after epithelialization) had a significantly higher density of microvessel and microcirculatory perfusion than those at the mature phase (day 90 after epithelization) (both p<0.05). On days 30 and 60 after treatment, the hypertrophic scar formation was significantly inhibited in the treatment group. There was significantly reduced scar elevation index, microvessel count, number of argyrophilic nucleolar organizer region, and total collagen content for treated scars. Our results demonstrate that METH1 has a markedly inhibitive effect on the formation of hypertrophic scar, and may thus have a promising application in the prevention of human hyperthropic scars.
authors.affiliation: Institute of Plastic Surgery, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaanxi 710032, China. songbq@fmmu.edu.cn
authors.forename: Baoqiang
authors.initials: B
authors.lastname: Song
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Shuzhong
authors.initials: S
authors.lastname: Guo
authors.forename: Yan
authors.initials: Y
authors.lastname: Han
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Fucheng
authors.initials: F
authors.lastname: Ma
authors.forename: Linxi
authors.initials: L
authors.lastname: Zhang
authors.forename: Kaihua
authors.initials: K
authors.lastname: Lu
mesh_terms: D051722:ADAM Proteins / Q000235:genetics / Q000502:physiology*; D000818:Animals; D017439:Cicatrix, Hypertrophic / Q000503:physiopathology* / Q000517:prevention & control; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D008833:Microcirculation; D009389:Neovascularization, Pathologic / Q000503:physiopathology* / Q000517:prevention & control; D011817:Rabbits; D012867:Skin / Q000098:blood supply*; D012883:Skin Ulcer / Q000235:genetics / Q000503:physiopathology; D014162:Transfection
chemical_list: D051722:ADAM Proteins