title: Down-Regulation of ClC-3 Expression Reduces Epidermal Stem Cell Migration by Inhibiting Volume-Activated Chloride Currents.
abstract: ClC-3, a member of the ClC chloride (Cl(-)) channel family, has recently been proposed as the primary Cl(-) channel involved in cell volume regulation. Changes in cell volume influence excitability, contraction, migration, pathogen-host interactions, cell proliferation, and cell death processes. In this study, expression and function of ClC-3 channels were investigated during epidermal stem cell (ESC) migration. We observed differential expression of CLC-3 regulates migration of ESCs. Further, whole-cell patch-clamp recordings and image analysis demonstrated ClC-3 expression affected volume-activated Cl(-) current (I Cl,Vol) within ESCs. Live cell imaging systems, designed to observe cellular responses to overexpression and suppression of ClC-3 in real time, indicated ClC-3 may regulate ESC migratory dynamics. We employed IMARIS software to analyze the velocity and distance of ESC migration in vitro to demonstrate the function of ClC-3 channel in ESCs. As our data suggest volume-activated Cl(-) channels play a vital role in migration of ESCs, which contribute to skin repair by migrating from neighboring unwounded epidermis infundibulum, hair follicle or sebaceous glands, ClC-3 may represent a new and valuable target for stem cell therapies.
authors.affiliation: Department of Plastic and Reconstructive Surgery, Southwestern Hospital, Third Military Medical University, Chongqing, 400038, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Guo
authors.affiliation: Department of Plastic and Reconstructive Surgery, Southwestern Hospital, Third Military Medical University, Chongqing, 400038, China.
authors.forename: Fuqiang
authors.initials: F
authors.lastname: Pan
authors.affiliation: Department of Histology and Embryology, Third Military Medical University, Chongqing, 400038, China.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Department of Histology and Embryology, Third Military Medical University, Chongqing, 400038, China.
authors.forename: Hongli
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Plastic and Reconstructive Surgery, Southwestern Hospital, Third Military Medical University, Chongqing, 400038, China. zxlishirong@yahoo.com.
authors.forename: Shirong
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Plastic and Reconstructive Surgery, Southwestern Hospital, Third Military Medical University, Chongqing, 400038, China. uccao@yahoo.com.
authors.forename: Chuan
authors.initials: C
authors.lastname: Cao
mesh_terms: D000818:Animals; D002460:Cell Line; D002465:Cell Movement / Q000235:genetics; D018118:Chloride Channels / Q000235:genetics* / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism*; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism*; D015870:Gene Expression; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D008297:Male; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D013234:Stem Cells / Q000378:metabolism*; D014161:Transduction, Genetic
chemical_list: D018118:Chloride Channels; D002712:Chlorides; C115376:ClC-3 channel; D012333:RNA, Messenger
keywords: Cell migration; ClC-3; Epidermal stem cell; Volume-activated chloride currents