Title: The proteoglycan versican binds the procollagen N‐propeptidase ADAMTS‐2 and regulates its activity
Abstract: The chondroitin sulfate proteoglycan versican is transiently expressed in developmental and remodeling processes where it is associated with cell migration and proliferation. Our previous studies have shown an accumulation of versican associated with proliferating myofibroblasts that synthesize type I procollagen in the fibroproliferative lesions of human fibrotic lung diseases. Collagen fibrillogenesis takes place in this versican-rich provisional matrix and versican is resorbed concomitant with collagen deposition. Thus we hypothesized that a type I collagen processing enzyme might contribute to versican degradation. Objectives: Investigate localization of versican and ADAMTS-2 in human lung biopsies and protein interactions in vitro. Methods: Immunohistochemical staining, versican and ADAMTS-2 purified from fibroblasts and ADAMTS-2 purified from fetal bovine skin. Results: versican and ADAMTS-2 co-localize in normal lungs and in sub-epithelial fibroblast foci in IPF; versican binds ADAMTS-2 in fetal lung fibroblast culture media; versican binding protects ADAMTS-2 from auto-degradation and versican is a substrate for ADAMTS-2 in vitro. Our data suggest that versican binding of ADAMTS-2 may localize this critical collagen-processing enzyme to fibroproliferative lesions and that ADAMTS-2 may mediate versican resorption. Supported by the CIHR and the BC Lung Association.
Publication Year: 2008
Publication Date: 2008-04-01
Language: en
Type: article
Indexed In: ['crossref']
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Cited By Count: 1
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