title: miR-155 promotes cutaneous wound healing through enhanced keratinocytes migration by MMP-2.
abstract: Inflammation, re-epithelization and tissue remodeling are three essential steps during wound healing. The re-epithelization process plays the most important role which mainly involves keratinocyte proliferation and migration. miR-155 has been reported to participate in cell migration and transformation, however, its function in skin wound healing is largely unknown. Here we hypothesize that overexpression of miR-155 at wound edges could accelerate wound healing mediated by enhanced keratinocyte migration. To test this hypothesis, direct local injection of miR-155 expression plasmid to wound edges was conducted to overexpress miR-155 in vivo. Results shown that miR-155 significantly promoted wound healing and re-epithelization compared to control, while did not affect wound contraction. Also, miR-155 overexpression accelerated primarily cultured keratinocyte migration in vitro, but had no effect on cell proliferation. Importantly, western blot analysis shown that MMP-2 was significantly upregulated whiles its inhibitor TIMP-1 downregulated after miR-155 treatment. Moreover, the use of ARP-101, an MMP-2 inhibitor, effectively attenuated the accelerative effects on cell migration induced by miR-155. Taken together, our results suggest that miR-155 has the promote effect on wound healing that is probably mediated by accelerating keratinocyte migration via upregulated MMP-2 level. This study provides a rationale for the therapeutic effect of miR-155 on wound healing.
authors.affiliation: Department of Burn and Plastic Surgery, The First Affiliated Hospital to PLA General Hospital, Beijing, China.
authors.forename: Longlong
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an, 710032, Shaanxi, China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an, 710032, Shaanxi, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an, 710032, Shaanxi, China.
authors.forename: Xiaozhi
authors.initials: X
authors.lastname: Bai
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an, 710032, Shaanxi, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Fan
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an, 710032, Shaanxi, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an, 710032, Shaanxi, China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Su
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an, 710032, Shaanxi, China. xjburnlab@126.com.
authors.forename: Dahai
authors.initials: D
authors.lastname: Hu
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D006801:Humans; D015603:Keratinocytes / Q000166:cytology*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000502:physiology*; D035683:MicroRNAs / Q000008:administration & dosage / Q000494:pharmacology*; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics; D012867:Skin; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000502:physiology; D014945:Wound Healing / Q000187:drug effects
chemical_list: C524942:MIRN155 microRNA, human; D035683:MicroRNAs; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2
keywords: Cell migration; MMP-2; MiR-155; Wound healing