Ultraviolet A Enhances Cathepsin L Expression and Activity via JNK Pathway in Human Dermal Fibroblasts.
- Author:
Qing-Fang XU
1
;
Yue ZHENG
1
;
Jian CHEN
1
;
Xin-Ya XU
1
;
Zi-Jian GONG
1
;
Yun-Fen HUANG
1
;
Chun LU
1
;
Howard I MAIBACH
2
;
Wei LAI
1
Author Information
- Publication Type:Journal Article
- MeSH: Anthracenes; pharmacology; Cathepsin L; metabolism; Cells, Cultured; Child; Child, Preschool; Enzyme Inhibitors; pharmacology; Extracellular Signal-Regulated MAP Kinases; antagonists & inhibitors; Fibroblasts; cytology; drug effects; metabolism; radiation effects; Humans; Imidazoles; pharmacology; MAP Kinase Signaling System; drug effects; radiation effects; Oncogene Proteins v-fos; genetics; metabolism; Proto-Oncogene Proteins c-jun; genetics; metabolism; Pyridines; pharmacology; Skin; cytology; Ultraviolet Rays
- From: Chinese Medical Journal 2016;129(23):2853-2860
- CountryChina
- Language:English
-
Abstract:
BACKGROUNDCathepsin 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).
METHODSPrimary 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.
RESULTSUVA 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.
CONCLUSIONSUVA 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.
