title: miR-21 regulates skin wound healing by targeting multiple aspects of the healing process.
abstract: With the clarification of the important roles of microRNAs (miRNAs) in diverse physiologic and pathologic processes, the effects of miRNAs in wound healing have attracted more attention recently. However, the global pattern of miRNA expression in wound tissue is still unknown. In the present study, we depicted the miRNA profile and identified at least 54 miRNAs, including miR-21, changed for more than twofold at the stage of granulation formation during wound healing. These miRNAs were closely related to the major events of wound healing, including cell migration and proliferation, angiogenesis, and matrix remolding. Furthermore, we found that miR-21 was up-regulated after skin injury, mainly in activated and migrating epithelial cells of epidermis and mesenchymal cells of dermis. Locally antagonizing miR-21 by directly injecting antagomir to wound edge caused significant delay of wound closure with impaired collagen deposition. Unexpectedly, we found wounds treated with miR-21 antagomir had an obvious defect in wound contraction at an early stage of wound healing. The significant role of miR-21 in wound contraction was further confirmed by in vivo gain-of-function and in vitro loss-of-function experiments. In conclusion, the present study has for the first time depicted miRNA profiling of wound healing and demonstrated the involvement of miR-21 in regulating the wound contraction and collagen deposition. These results suggest that miR-21 may be a new medical target in skin wound manipulation.
authors.affiliation: Institute of Combined Injury, State Key Laboratory of Trauma, Burn and Combined Injury, College of Preventive Medicine, Third Military Medical University, Chongqing, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Yimei
authors.initials: Y
authors.lastname: Feng
authors.forename: Huiqin
authors.initials: H
authors.lastname: Sun
authors.forename: Lilong
authors.initials: L
authors.lastname: Zhang
authors.forename: Lei
authors.initials: L
authors.lastname: Hao
authors.forename: Chunmeng
authors.initials: C
authors.lastname: Shi
authors.forename: Junping
authors.initials: J
authors.lastname: Wang
authors.forename: Rong
authors.initials: R
authors.lastname: Li
authors.forename: Xinze
authors.initials: X
authors.lastname: Ran
authors.forename: Yongping
authors.initials: Y
authors.lastname: Su
authors.forename: Zhongmin
authors.initials: Z
authors.lastname: Zou
mesh_terms: D000818:Animals; D003094:Collagen / Q000378:metabolism; D020869:Gene Expression Profiling; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D012867:Skin / Q000378:metabolism* / Q000473:pathology*; D015854:Up-Regulation / Q000235:genetics; D014945:Wound Healing / Q000235:genetics*
chemical_list: C531950:MIRN21 microRNA, mouse; D035683:MicroRNAs; D003094:Collagen