title: Ultraviolet A-induced cathepsin K expression is mediated via MAPK/AP-1 pathway in human dermal fibroblasts.
abstract: BACKGROUND
  Cathepsin K (CatK), a cysteine protease with the potent elastolytic activity, plays a predominant role in intracellular elastin degradation in human dermal fibroblasts (HDFs), and contributes to solar elastosis. In previous studies, CatK expression was downregulated in photoaged skin and fibroblasts, but upregulated in acute UVA-irradiated skin and fibroblasts. The underlying mechanisms regulating UVA-induced CatK expression remain elusive.
  
  
  OBJECTIVE
  This study investigates mechanisms involved in the regulation of UVA-induced CatK expression in HDFs.
  
  
  METHODS
  Primary HDFs were exposed to UVA. Cell proliferation was analyzed using a colorimetric assay of relative cell number. Quantitative real-time RT-PCR and Western blot were performed to detect CatK expression in HDFs on three consecutive days after 10 J/cm2 UVA irradiation, or cells treated with increasing UVA doses. UVA-activated MAPK/AP-1 pathway was examined by Western blot. Effects of inhibition of MAPK pathway and knockdown of Jun and Fos on UVA-induced CatK expression were also measured by real-time RT-PCR and Western blot.
  
  
  RESULTS
  UVA significantly increased CatK mRNA and protein expression in a dose-dependent manner. UVA-induced CatK expression occurred along with UVA-activated phosphorylation of JNK, p38 and Jun, UVA-increased expression of Fos. Inactivation of JNK and p38MAPK pathways both remarkably decreased UVA-induced CatK expression, which was suppressed more by inhibition of JNK pathway. Furthermore, knockdown of Jun and Fos significantly attenuated basal and UVA-induced CatK expression.
  
  
  CONCLUSIONS
  UVA is capable of increasing CatK expression in HDFs, most likely by activation of MAPK pathway and of AP-1, which has been shown to be the case for matrix metalloproteinases. As current strategies for selecting anti-photoaging agents focus on their ability to decrease MMPs' expression through inhibiting UV- activated MAPK pathway, future strategies should also consider their effect on CatK expression.
authors.affiliation: Department of Dermato-Venereology, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, PR China.
authors.forename: Qingfang
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Department of Dermato-Venereology, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, PR China; Department of Dermato-Venereology, the First Teaching hospital of Xinjiang Medical University, Urumqi, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Hou
authors.affiliation: Department of Dermato-Venereology, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, PR China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Dermato-Venereology, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, PR China.
authors.forename: Chen
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Dermato-Venereology, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, PR China.
authors.forename: Zijian
authors.initials: Z
authors.lastname: Gong
authors.affiliation: Department of Dermato-Venereology, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, PR China.
authors.forename: Chun
authors.initials: C
authors.lastname: Lu
authors.affiliation: Department of Dermato-Venereology, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Lai
authors.affiliation: Department of Dermatology, School of Medicine, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Howard I
authors.initials: HI
authors.lastname: Maibach
mesh_terms: D056657:Cathepsin K / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D002648:Child; D004307:Dose-Response Relationship, Radiation; D005347:Fibroblasts / Q000378:metabolism* / Q000528:radiation effects; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology / Q000528:radiation effects*; D008297:Male; D010766:Phosphorylation; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D012867:Skin / Q000378:metabolism* / Q000528:radiation effects; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014466:Ultraviolet Rays
chemical_list: D016760:Proto-Oncogene Proteins c-fos; D018808:Transcription Factor AP-1; D056657:Cathepsin K