title: MicroRNA expression signature and the therapeutic effect of the microRNA‑21 antagomir in hypertrophic scarring.
abstract: Hypertrophic scars (HS) area fibroproliferative disorder of the skin, which causes aesthetic and functional impairment. However, the molecular pathogenesis of this disease remains largely unknown and currently no efficient treatment exists. MicroRNAs (miRNAs) are involved in a variety of pathophysiological processes, however the role of miRNAs in HS development remains unclear. To investigate the miRNA expression signature of HS, microarray analysis was performed and 152 miRNAs were observed to be differentially expressed in HS tissue compared with normal skin tissues. Of the miRNAs identified, miRNA‑21 (miR‑21) was significantly increased in HS tissues and hypertrophic scar fibroblasts (HSFBs) as determined by reverse transcription‑quantitative polymerase chain reaction analysis. It was also observed that, when miR‑21 in HSFBs was blocked through use of an antagomir, the phenotype of fibrotic fibroblasts in vitro was reversed, as demonstrated by growth inhibition, induction of apoptosis and suppressed expression of fibrosis‑associated genes collagen type I α 1 chain (COL1A1), COL1A2 and fibronectin. Furthermore, miR‑21 antagomir administration significantly reduced the severity of HS formation and decreased collagen deposition in a rabbit ear HS model. The total scar area and scar elevation index were calculated and were demonstrated to be significantly decreased in the treatment group compared with control rabbits. These results indicated that the miR‑21 antagomir has a therapeutic effect on HS and suggests that targeting miRNAs may be a successful and novel therapeutic strategy in the treatment of fibrotic diseases that are difficult to treat with existing methods.
authors.affiliation: Department of Plastic Surgery, Wuhan General Hospital of Guangzhou Military Command of Chinese PLA, Wuhan, Hubei 430070, P.R. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Guo
authors.affiliation: Department of Plastic Surgery, Wuhan General Hospital of Guangzhou Military Command of Chinese PLA, Wuhan, Hubei 430070, P.R. China.
authors.forename: Kai
authors.initials: K
authors.lastname: Xu
authors.affiliation: Department of Plastic Surgery, Wuhan General Hospital of Guangzhou Military Command of Chinese PLA, Wuhan, Hubei 430070, P.R. China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Yan
authors.affiliation: Department of Plastic Surgery, Wuhan General Hospital of Guangzhou Military Command of Chinese PLA, Wuhan, Hubei 430070, P.R. China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Feng
authors.affiliation: Institute of Combined Injury, State Key Laboratory of Trauma, Burn and Combined Injury, Third Military Medical University, Chongqing 400038, P.R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Plastic and Reconstructive Surgery, Southwestern Hospital, Third Military Medical University, Chongqing 400038, P.R. China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Chai
authors.affiliation: Department of Neurosurgery, Wuhan General Hospital of Guangzhou Military Command of Chinese PLA, Wuhan, Hubei 430070, P.R. China.
authors.forename: Guozheng
authors.initials: G
authors.lastname: Xu
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000070416:Antagomirs / Q000235:genetics*; D017209:Apoptosis; D002460:Cell Line; D017439:Cicatrix, Hypertrophic / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D016000:Cluster Analysis; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D000090602:Collagen Type I, alpha 1 Chain; D004195:Disease Models, Animal; D005355:Fibrosis; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D011817:Rabbits; D059467:Transcriptome; D055815:Young Adult
chemical_list: D000070416:Antagomirs; C000716127:COL1A1 protein, human; D000090602:Collagen Type I, alpha 1 Chain; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D003094:Collagen