title: Alternate trafficking of cathepsin L in dermal fibroblasts induced by UVA radiation.
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.
authors.affiliation: Department of Dermatology, University of Cologne, Cologne, Germany. anke.klose@uk-koeln.de
authors.forename: Anke
authors.initials: A
authors.lastname: Klose
authors.forename: Astrid
authors.initials: A
authors.lastname: Wilbrand-Hennes
authors.forename: Jürgen
authors.initials: J
authors.lastname: Brinckmann
authors.forename: Nicolas
authors.initials: N
authors.lastname: Hunzelmann
mesh_terms: D056668:Cathepsin L / Q000378:metabolism*; D002478:Cells, Cultured; D003238:Connective Tissue / Q000378:metabolism; D020405:Dermis / Q000166:cytology / Q000378:metabolism* / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D004792:Enzyme Precursors / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism* / Q000528:radiation effects; D006801:Humans; D021381:Protein Transport / Q000528:radiation effects*; D014466:Ultraviolet Rays
chemical_list: D004792:Enzyme Precursors; C063905:procathepsin L; D056668:Cathepsin L