期刊
EXPERIMENTAL DERMATOLOGY
卷 19, 期 8, 页码 E117-E123出版社
WILEY
DOI: 10.1111/j.1600-0625.2009.01014.x
关键词
cathepsin L; lysosomal protease; secretion; UVA; zymography
类别
资金
- BMBF [01 GM 0630]
- Koln Fortune program
- DFG [Br 1146/3-3]
UVA radiation is increasingly used to treat fibrotic skin disorders. However, the mechanisms underlying the therapeutic effects of UVA for these disorders are only partially understood. Cathepsin L is a lysosomal cysteine protease, which has been shown to degrade various matrix proteins thus contributing to extracellular remodeling. Therefore, we investigated whether UVA irradiation regulates the expression and release of cathepsin L in human dermal fibroblasts. No alterations were found after single irradiation; however, a significantly increased extracellular release of cathepsin L was observed after repeated irradiation up to four times. The transcript levels of cathepsin L were elevated after repetitive irradiation, leading to increased amounts of total cathepsin L protein. Furthermore, higher amounts of extracellular cathepsin L were associated with a significant reduction of intracellular processed cathepsin L and an accumulation of unprocessed procathepsin L. The use of specific inhibitors elucidated mannose phosphate-independent sorting pathways of cathepsin L leading to enhanced secretion and reduced intracellular processing. This is the first study which demonstrates that alternate trafficking mechanisms mediate the extracellular release of a cysteine protease induced by repetitive UVA irradiation.
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