title: P311 Accelerates Skin Wound Reepithelialization by Promoting Epidermal Stem Cell Migration Through RhoA and Rac1 Activation.
abstract: P311 is a newly discovered functional gene, and it has been proved to play a key role in blood pressure homeostasis, glioblastoma invasion, renal fibrosis, hypertrophic scar formation, and others. In this study, for the first time, we found that P311 could enhance reepithelialization during wound healing via promoting epidermal stem cell (EpSC) migration through Rho GTPases. P311 expression was highly increased in neo-epidermal cells during human and mouse skin wound healing, and P311was co-localized with 5-bromo-2'-deoxyuridine positive label-retaining cells in a mouse superficial second-degree burn wound model. Furthermore, transfection of human EpSCs with adenovirus encoding P311 significantly accelerated the cell migration in vitro. Moreover, highly expressed P311 could enhance the activities of the Rho GTPases (RhoA, Rac1, and Cdc42) in cultured human EpSCs. P311-knockout mouse EpSCs showed dramatically decreased cell migration and activities of Rho GTPases (RhoA, Rac1, and Cdc42). Besides, both the RhoA-specific inhibitor and the Rac1 inhibitor, not the Cdc42 inhibitor, could significantly suppress P311-induced human EpSC migration. In vivo, the reepithelialization was markedly impaired during wound healing after P311 was knocked out. Together, our results suggested that P311 could accelerate skin wound reepithelialization by promoting the migration of EpSCs through RhoA and Rac1 activation. P311 could serve as a novel target for regulation of EpSC migration during cutaneous wound healing.
authors.affiliation: 1 State Key Laboratory of Trauma, Burn and Combined Injury, Institute of Burn Research, Southwest Hospital, Third Military Medical University , Chongqing, China .|2 People's Liberation Army Hospital 59 , Kaiyuan, China .
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Yao
authors.affiliation: 1 State Key Laboratory of Trauma, Burn and Combined Injury, Institute of Burn Research, Southwest Hospital, Third Military Medical University , Chongqing, China .
authors.forename: Haisheng
authors.initials: H
authors.lastname: Li
authors.affiliation: 1 State Key Laboratory of Trauma, Burn and Combined Injury, Institute of Burn Research, Southwest Hospital, Third Military Medical University , Chongqing, China .
authors.forename: Weifeng
authors.initials: W
authors.lastname: He
authors.affiliation: 1 State Key Laboratory of Trauma, Burn and Combined Injury, Institute of Burn Research, Southwest Hospital, Third Military Medical University , Chongqing, China .
authors.forename: Sisi
authors.initials: S
authors.lastname: Yang
authors.affiliation: 1 State Key Laboratory of Trauma, Burn and Combined Injury, Institute of Burn Research, Southwest Hospital, Third Military Medical University , Chongqing, China .
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: 1 State Key Laboratory of Trauma, Burn and Combined Injury, Institute of Burn Research, Southwest Hospital, Third Military Medical University , Chongqing, China .
authors.forename: Rixing
authors.initials: R
authors.lastname: Zhan
authors.affiliation: 1 State Key Laboratory of Trauma, Burn and Combined Injury, Institute of Burn Research, Southwest Hospital, Third Military Medical University , Chongqing, China .
authors.forename: Rui
authors.initials: R
authors.lastname: Xu
authors.affiliation: 1 State Key Laboratory of Trauma, Burn and Combined Injury, Institute of Burn Research, Southwest Hospital, Third Military Medical University , Chongqing, China .
authors.forename: Jianglin
authors.initials: J
authors.lastname: Tan
authors.affiliation: 1 State Key Laboratory of Trauma, Burn and Combined Injury, Institute of Burn Research, Southwest Hospital, Third Military Medical University , Chongqing, China .
authors.forename: Junyi
authors.initials: J
authors.lastname: Zhou
authors.affiliation: 1 State Key Laboratory of Trauma, Burn and Combined Injury, Institute of Burn Research, Southwest Hospital, Third Military Medical University , Chongqing, China .
authors.forename: Jun
authors.initials: J
authors.lastname: Wu
authors.affiliation: 1 State Key Laboratory of Trauma, Burn and Combined Injury, Institute of Burn Research, Southwest Hospital, Third Military Medical University , Chongqing, China .
authors.forename: Gaoxing
authors.initials: G
authors.lastname: Luo
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002465:Cell Movement / Q000187:drug effects; D002648:Child; D004789:Enzyme Activation / Q000187:drug effects; D004817:Epidermis / Q000473:pathology*; D006801:Humans; D008297:Male; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000378:metabolism*; D015513:Oncogene Proteins / Q000378:metabolism*; D009930:Organic Chemicals / Q000494:pharmacology; D062326:Re-Epithelialization / Q000187:drug effects; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
chemical_list: C428027:NREP protein, human; D009419:Nerve Tissue Proteins; D015513:Oncogene Proteins; D009930:Organic Chemicals; C530930:P311 protein, mouse; C586690:rhosin; D020830:rac1 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein
keywords: P311; Rho GTPases; epidermal stem cell; migration; wound reepithelialization