title: Ultraviolet A Enhances Cathepsin L Expression and Activity via JNK Pathway in Human Dermal Fibroblasts.
abstract: BACKGROUND
  Cathepsin L (CatL) is a cysteine protease with strong matrix degradation activity that contributes to photoaging. Mannose phosphate-independent sorting pathways mediate ultraviolet A (UVA)-induced alternate trafficking of CatL. Little is known about signaling pathways involved in the regulation of UVA-induced CatL expression and activity. This study aims to investigate whether a single UVA irradiation affects CatL expression and activity and whether mitogen-activated protein kinase (MAPK)/activator protein-1 (AP-1) pathway is involved in the regulation of UVA-induced CatL expression and activity in human dermal fibroblasts (HDFs).
  
  
  METHODS
  Primary HDFs were exposed to UVA. Cell proliferation was determined by a cell counting kit. UVA-induced CatL production and activity were studied with quantitative real-time reverse transcription polymerase chain reaction (RT-PCR), Western blotting, and fluorimetric assay in cell lysates collected on three consecutive days after irradiation. Time courses of UVA-activated JNK and p38MAPK signaling were examined by Western blotting. Effects of MAPK inhibitors and knockdown of Jun and Fos on UVA-induced CatL expression and activity were investigated by RT-PCR, Western blotting, and fluorimetric assay. Data were analyzed by one-way analysis of variance.
  
  
  RESULTS
  UVA significantly increased CatL gene expression, protein abundance, and enzymatic activity for three consecutive days after irradiation (F = 83.11, 56.14, and 71.19, respectively; all P < 0.05). Further investigation demonstrated phosphorylation of JNK and p38MAPK activated by UVA. Importantly, inactivation of JNK pathway significantly decreased UVA-induced CatL expression and activity, which were not affected by p38MAPK inhibition. Moreover, knockdown of Jun and Fos significantly attenuated basal and UVA-induced CatL expression and activity.
  
  
  CONCLUSIONS
  UVA enhances CatL production and activity in HDFs, probably by activating JNK and downstreaming AP-1. These findings provide a new possible molecular approach for antiphotoaging therapy.
authors.affiliation: Department of Dermato-Venereology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510630, China.
authors.forename: Qing-Fang
authors.initials: QF
authors.lastname: Xu
authors.affiliation: Department of Dermato-Venereology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510630, 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, Guangdong 510630, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Dermato-Venereology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510630, China.
authors.forename: Xin-Ya
authors.initials: XY
authors.lastname: Xu
authors.affiliation: Department of Dermato-Venereology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510630, China.
authors.forename: Zi-Jian
authors.initials: ZJ
authors.lastname: Gong
authors.affiliation: Department of Dermato-Venereology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510630, China.
authors.forename: Yun-Fen
authors.initials: YF
authors.lastname: Huang
authors.affiliation: Department of Dermato-Venereology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510630, China.
authors.forename: Chun
authors.initials: C
authors.lastname: Lu
authors.affiliation: Department of Dermatology, School of Medicine, University of California, San Francisco, CA 94143, USA.
authors.forename: Howard I
authors.initials: HI
authors.lastname: Maibach
authors.affiliation: Department of Dermato-Venereology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510630, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Lai
mesh_terms: D000873:Anthracenes / Q000494:pharmacology; D056668:Cathepsin L / Q000378:metabolism*; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000528:radiation effects; D016761:Oncogene Proteins v-fos / Q000235:genetics / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D012867:Skin / Q000166:cytology*; D014466:Ultraviolet Rays
chemical_list: D000873:Anthracenes; D004791:Enzyme Inhibitors; D007093:Imidazoles; D016761:Oncogene Proteins v-fos; D016755:Proto-Oncogene Proteins c-jun; D011725:Pyridines; C432165:pyrazolanthrone; D048049:Extracellular Signal-Regulated MAP Kinases; D056668:Cathepsin L; C093642:SB 203580