title: Nitric oxide promotes epidermal stem cell migration via cGMP-Rho GTPase signalling.
abstract: The migration and reepithelization of epidermal stem cells (ESCs) are the most critical processes in wound healing. The gaseous messenger nitric oxide (NO) has multiple biological effects, but its actions on ESCs are poorly understood. In this study, an NO donor, S-nitroso-N-acetylpenicillamine (SNAP), was found to facilitate the in vitro migration of human ESCs (huESCs) in both live-imaging and scratch models. In addition, pull-down assays demonstrated that SNAP could activate the small GTPases RhoA and Rac1 of the Rho family, but not Cdc42. Moreover, the effects of SNAP on the migration and F-actin polymerization of ESCs could be blocked by inhibitors of cGMP, PKG, RhoA or Rac1, and by a specific siRNA of RhoA or Rac1, but not by a Cdc42 inhibitor or siRNA. Furthermore, the roles of NO in ESC migration via cGMP-Rho GTPase signalling in vivo were confirmed by tracing 5-bromo-2-deoxyuridine (BrdU)-labelled cells in a superficial, partial-thickness scald mouse model. Thus, the present study demonstrated that the NO donor SNAP could promote huESC migration in vitro. Furthermore, NO was found to induce ESC migration via cGMP-Rho GTPase RhoA and Rac1 signalling, but not Cdc42 signalling, both in vivo and in vitro.
authors.affiliation: Institute of Burn Research; State Key Laboratory of Trauma, Burn and Combined Injury; Key Laboratory of Proteomics of Chongqing, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Rixing
authors.initials: R
authors.lastname: Zhan
authors.affiliation: Institute of Burn Research; State Key Laboratory of Trauma, Burn and Combined Injury; Key Laboratory of Proteomics of Chongqing, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Weifeng
authors.initials: W
authors.lastname: He
authors.affiliation: Institute of Burn Research; State Key Laboratory of Trauma, Burn and Combined Injury; Key Laboratory of Proteomics of Chongqing, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Wang
authors.affiliation: Institute of Burn Research; State Key Laboratory of Trauma, Burn and Combined Injury; Key Laboratory of Proteomics of Chongqing, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Yao
authors.affiliation: Institute of Burn Research; State Key Laboratory of Trauma, Burn and Combined Injury; Key Laboratory of Proteomics of Chongqing, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Jianglin
authors.initials: J
authors.lastname: Tan
authors.affiliation: Institute of Burn Research; State Key Laboratory of Trauma, Burn and Combined Injury; Key Laboratory of Proteomics of Chongqing, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Xu
authors.affiliation: Institute of Burn Research; State Key Laboratory of Trauma, Burn and Combined Injury; Key Laboratory of Proteomics of Chongqing, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Junyi
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Institute of Burn Research; State Key Laboratory of Trauma, Burn and Combined Injury; Key Laboratory of Proteomics of Chongqing, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Yuzhen
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Institute of Burn Research; State Key Laboratory of Trauma, Burn and Combined Injury; Key Laboratory of Proteomics of Chongqing, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Haisheng
authors.initials: H
authors.lastname: Li
authors.affiliation: Institute of Burn Research; State Key Laboratory of Trauma, Burn and Combined Injury; Key Laboratory of Proteomics of Chongqing, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wu
authors.affiliation: Institute of Burn Research; State Key Laboratory of Trauma, Burn and Combined Injury; Key Laboratory of Proteomics of Chongqing, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Gaoxing
authors.initials: G
authors.lastname: Luo
mesh_terms: D000199:Actins / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism*; D004817:Epidermis / Q000187:drug effects*; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism*; D055503:Protein Multimerization; D015398:Signal Transduction; D013234:Stem Cells / Q000187:drug effects* / Q000502:physiology; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
chemical_list: D000199:Actins; D009569:Nitric Oxide; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein; D006152:Cyclic GMP