title: Downregulation of miR-205 in migrating epithelial tongue facilitates skin wound re-epithelialization by derepressing ITGA5.
abstract: Keratinocyte migration is essential for re-epithelialization during skin wound healing, but the molecular mechanisms regulating this cellular response remain to be completely clarified. Here we show that keratinocyte-specific miR-205 is significantly downregulated in the leading edge of the migrating epithelial tongue after skin injury in mice. In HaCaT keratinocytes, miR-205 could be downregulated by TGF-β1 stimulation. And similar to the effect of TGF-β1, miR-205 knockdown could promote keratinocyte migration in wound scratch model in vitro. Furthermore, topical inhibition of miR-205 by administrating Pluronic gel containing antagomir-205 could accelerate re-epithelialization in mouse skin wound model in vivo. Moreover, we identified integrin alpha 5 (ITGA5) as one key functional miR-205 target in the re-epithelialization process and epidermal downregulation of miR-205 may desilence ITGA5 to promote keratinocyte migration. And knockdown of ITGA5 would abolish the pro-migratory effects of miR-205 inhibition in vitro. What's more, we found dysregulation of miR-205 and its target ITGA5 in epidermis of clinical chronic wound samples with persistence of high level miR-205 and absence of ITGA5. Our findings indicate that downregulation of miR-205 in the leading migrating keratinocytes is critical for re-epithelialization and miR-205 may be a potential therapeutic target for chronic wounds.
authors.affiliation: Institute of Combined Injury, State Key Laboratory of Trauma, Burn and Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, Chongqing 400038, China. Electronic address: wangtmmu@hotmail.com.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Institute of Combined Injury, State Key Laboratory of Trauma, Burn and Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, Chongqing 400038, China.
authors.forename: Na
authors.initials: N
authors.lastname: Zhao
authors.affiliation: Institute of Combined Injury, State Key Laboratory of Trauma, Burn and Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, Chongqing 400038, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Long
authors.affiliation: Department of Dermatology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Ge
authors.affiliation: Institute of Combined Injury, State Key Laboratory of Trauma, Burn and Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, Chongqing 400038, China.
authors.forename: Aiping
authors.initials: A
authors.lastname: Wang
authors.affiliation: Institute of Combined Injury, State Key Laboratory of Trauma, Burn and Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, Chongqing 400038, China.
authors.forename: Huiqin
authors.initials: H
authors.lastname: Sun
authors.affiliation: Institute of Combined Injury, State Key Laboratory of Trauma, Burn and Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, Chongqing 400038, China.
authors.forename: Xinze
authors.initials: X
authors.lastname: Ran
authors.affiliation: Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing 400038, China.
authors.forename: Zhongmin
authors.initials: Z
authors.lastname: Zou
authors.affiliation: Institute of Combined Injury, State Key Laboratory of Trauma, Burn and Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, Chongqing 400038, China.
authors.forename: Junping
authors.initials: J
authors.lastname: Wang
authors.affiliation: Institute of Combined Injury, State Key Laboratory of Trauma, Burn and Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, Chongqing 400038, China. Electronic address: suyp2003@163.com.
authors.forename: Yongping
authors.initials: Y
authors.lastname: Su
mesh_terms: D000818:Animals; D002465:Cell Movement; D004195:Disease Models, Animal; D006801:Humans; D039482:Integrin alpha5 / Q000235:genetics / Q000378:metabolism*; D015603:Keratinocytes / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009061:Mouth Mucosa / Q000293:injuries* / Q000378:metabolism / Q000473:pathology; D014059:Tongue / Q000293:injuries* / Q000378:metabolism / Q000473:pathology; D014945:Wound Healing
chemical_list: D039482:Integrin alpha5; C576666:MIRN205 microRNA, mouse; D035683:MicroRNAs
keywords: Chronic wounds; ITGA5; Re-epithelialization; Wound healing; miR-205