title: Dynamically Regulated CFTR Expression and Its Functional Role in Cutaneous Wound Healing.
abstract: The physiological role of cystic fibrosis transmembrane conductance regulator (CFTR) in keratinocytes and skin wound healing is completely unknown. The present study shows that CFTR is expressed in the multiple layers of keratinocytes in mouse epidermis and exhibits a dynamic expression pattern in a dorsal skin wound healing model, with diminishing levels observed from day 3 to day 5 and re-appearing from day 7 to day 10 after wounding. Knockdown of CFTR in cultured human keratinocytes promotes cell migration but inhibits differentiation, while overexpression of CFTR suppresses migration but enhances differentiation, indicating an important role of CFTR in regulating keratinocyte behavior. In addition, we have demonstrated a direct association of CFTR with epithelial junction formation as knockdown of CFTR downregulates the expression of adhesion molecules, such as E-cadherin, ZO-1 and β-catenin, and disrupts the formation of cell junction, while overexpression of CFTR enhances cell junction formation. More importantly, we have shown that ΔF508cftr-/- mice with defective CFTR exhibit delayed wound healing as compared to wild type mice, indicating that normal function of CFTR is critical for wound repair. Taken together, the present study has revealed a previously undefined role of CFTR in regulating skin wound healing processes, which may have implications in injury repair of other epithelial tissues.
authors: School of Life Sciences, Sun Yat-sen University, Guangzhou, China.|Epithelial Cell Biology Research Center, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, NT, Hong Kong.|Key Laboratory of Reproduction and Genetic of Ningxia Hui Autonomous Region, Key Laboratory of Fertility Preservation and Maintenance of Ningxia Medical University and Ministry of Education of China, Yinchuan, China.
authors: Jianda
authors: J
authors: Dong
authors: Epithelial Cell Biology Research Center, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, NT, Hong Kong.|Key Laboratory for Regenerative Medicine (Ji Nan University - The Chinese University of Hong Kong), Ministry of Education of the People's Republic of China, China.
authors: Xiaohua
authors: X
authors: Jiang
authors: Epithelial Cell Biology Research Center, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, NT, Hong Kong.
authors: Xiaohu
authors: X
authors: Zhang
authors: Epithelial Cell Biology Research Center, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, NT, Hong Kong.
authors: Kai Sheng
authors: KS
authors: Liu
authors: Epithelial Cell Biology Research Center, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, NT, Hong Kong.
authors: Jieting
authors: J
authors: Zhang
authors: Epithelial Cell Biology Research Center, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, NT, Hong Kong.|Sichuan University - The Chinese University of Hong Kong Joint Laboratory for Reproductive Medicine, West China Second University Hospital, Chengdu, China.
authors: Jing
authors: J
authors: Chen
authors: Epithelial Cell Biology Research Center, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, NT, Hong Kong.
authors: Mei Kuen
authors: MK
authors: Yu
authors: Epithelial Cell Biology Research Center, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, NT, Hong Kong.
authors: Lai Ling
authors: LL
authors: Tsang
authors: Epithelial Cell Biology Research Center, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, NT, Hong Kong.
authors: Yiu Wa
authors: YW
authors: Chung
authors: Key Laboratory of Reproduction and Genetic of Ningxia Hui Autonomous Region, Key Laboratory of Fertility Preservation and Maintenance of Ningxia Medical University and Ministry of Education of China, Yinchuan, China.
authors: Yanrong
authors: Y
authors: Wang
authors: School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
authors: Wen-Liang
authors: WL
authors: Zhou
authors: Epithelial Cell Biology Research Center, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, NT, Hong Kong.|Key Laboratory for Regenerative Medicine (Ji Nan University - The Chinese University of Hong Kong), Ministry of Education of the People's Republic of China, China.|Sichuan University - The Chinese University of Hong Kong Joint Laboratory for Reproductive Medicine, West China Second University Hospital, Chengdu, China.
authors: Hsiao Chang
authors: HC
authors: Chan
mesh_terms: D000818:Animals; D015820:Cadherins / Q000096:biosynthesis; D002454:Cell Differentiation / Q000235:genetics*; D002460:Cell Line; D002465:Cell Movement / Q000235:genetics; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000096:biosynthesis / Q000235:genetics*; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology; D051379:Mice; D012867:Skin / Q000293:injuries / Q000378:metabolism* / Q000473:pathology; D014945:Wound Healing / Q000235:genetics*; D051176:beta Catenin / Q000096:biosynthesis
chemical_list: D015820:Cadherins; D051176:beta Catenin; D019005:Cystic Fibrosis Transmembrane Conductance Regulator