Alternate trafficking of cathepsin L in dermal fibroblasts induced by UVA radiation |
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Authors: | Anke Klose Astrid Wilbrand‐Hennes Jürgen Brinckmann Nicolas Hunzelmann |
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Affiliation: | 1. Department of Dermatology, University of Cologne, Cologne, Germany;2. Department of Dermatology, University of Lübeck, Lübeck, Germany |
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Abstract: | Please cite this paper as: Alternate trafficking of cathepsin L in dermal fibroblasts induced by UVA radiation. Experimental Dermatology 2010; 19 : e117–e123. Abstract: 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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Keywords: | cathepsin L lysosomal protease secretion UVA zymography |
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