title: Ski, a modulator of wound healing and scar formation in the rat skin and rabbit ear.
abstract: We recently demonstrated that Ski is a novel wound healing-related factor that promotes fibroblast proliferation and inhibits collagen secretion. Here, we show that increasing local Ski expression by gene transfer not only significantly accelerated wound healing by relieving inflammation, accelerating re-epithelialization and increasing formation of granulation tissue, but also reduced scar formation by decreasing collagen production in rat dermal wounds. Similarly, ski gene transfer accelerated wound healing, reduced the protuberant height and volume of scars and increased collagen maturity in a hypertrophic scar model in the rabbit ear. Conversely, reducing Ski expression in the wound by RNA interference resulted in significantly slower wound healing and increased scar area in rat dermal wounds. We demonstrated that these effects of Ski are associated with transforming growth factor-β-mediated signalling pathways through both Smad2/3-dependent and Smad-independent pathways. Together, our results define a dual role for Ski in promoting wound healing and alleviating scar formation, identifying a new target for therapeutic approaches to preventing scar hyperplasia and accelerating wound healing.
authors.affiliation: The Molecular Biology Centre, State Key Laboratory of Trauma, Burn and Combined Injury, Research Institute of Surgery and Daping Hospital, Third Military Medical University, 10 Changjiang Zhilu, Chongqing, People's Republic of China.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.forename: Ren-Ping
authors.initials: RP
authors.lastname: Xiong
authors.forename: Xing-Yun
authors.initials: XY
authors.lastname: Chen
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Lu
authors.forename: Xia
authors.initials: X
authors.lastname: Liu
authors.forename: Ya-Lei
authors.initials: YL
authors.lastname: Ning
authors.forename: Nan
authors.initials: N
authors.lastname: Yang
authors.forename: Yuan-Guo
authors.initials: YG
authors.lastname: Zhou
mesh_terms: D000818:Animals; D002921:Cicatrix / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy; D017439:Cicatrix, Hypertrophic / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D003094:Collagen / Q000378:metabolism; D004431:Ear, External / Q000293:injuries; D005260:Female; D005786:Gene Expression Regulation; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D034622:RNA Interference; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000293:injuries; D014945:Wound Healing / Q000502:physiology*
chemical_list: D018836:Inflammation Mediators; D011518:Proto-Oncogene Proteins; C525545:Ski protein, rat; D003094:Collagen