Expression and regulation of cathepsin K in skin fibroblasts.
Cathepsin K (catK) is a lysosomal cysteine protease with strong collagenolytic activity well known to mediate bone resorption in osteoclasts. Recently, catK has also been reported to be expressed in other tissues. In the dermis, it is expressed only under certain circumstances such as scarring or inflammation. We therefore investigated the expression and regulation of this protease in dermal fibroblasts using immunoblotting and immunostaining. Cultured skin fibroblasts were found to strongly express catK in lysosomes. Internalization of collagen I and IV to lysosomes of fibroblasts indicates a role of catK in intracellular collagen degradation after endocytosis, a process that is different from the metalloproteinase-mediated collagen degradation in the extracellular space. In fibroblasts, interleukin-1alpha and cellular confluence upregulate catK expression and transforming growth factor-beta1 inhibits confluence-induced catK upregulation in skin fibroblasts. RANKL (ligand of receptor activator of NF-kappaB) did not alter catK expression. These regulators of catK expression are likely to play a role in the as-needed upregulation in certain skin conditions, where the prominent matrix-degrading properties of catK are thought to require tight regulation to maintain the homeostasis of the extracellular matrix.
Quintanilla-Dieck
Maria J
MJ
Department of Dermatology, Boston University School of Medicine, Boston, MA 02118, USA.
Codriansky
Katerine
K
Keady
Michelle
M
Bhawan
Jag
J
Rünger
Thomas M
TM
D056657:Cathepsin K; D002403:Cathepsins / Q000378:metabolism*; D002452:Cell Count; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D024141:Collagen Type IV / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D053582:Interleukin-1alpha / Q000494:pharmacology; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D008544:Melanocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D053245:RANK Ligand / Q000494:pharmacology; D012867:Skin / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology
D024042:Collagen Type I; D024141:Collagen Type IV; D053582:Interleukin-1alpha; D053245:RANK Ligand; D053773:Transforming Growth Factor beta1; D002403:Cathepsins; C534130:CTSK protein, human; D056657:Cathepsin K