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 altate 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),West 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 West blotting.Effects ofMAPK inhibitors and knockdown of Jun and Fos on UVA-induced CatL expression and activity were investigated by RT-PCR,West 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.