Fibronectin matrix turnover occurs through a caveolin-1-dependent process.
Extracellular matrix remodeling occurs during development, tissue repair, and in a number of pathologies, including fibrotic disorders, hypertension, and atherosclerosis. Extracellular matrix remodeling involves the complex interplay between extracellular matrix synthesis, deposition, and degradation. Factors that control these processes are likely to play key roles in regulating physiological and pathological extracellular matrix remodeling. Our data show that fibronectin polymerization into the extracellular matrix regulates the deposition and stability of other extracellular matrix proteins, including collagen I and thrombospondin-1 (Sottile and Hocking, 2002. Mol. Biol. Cell 13, 3546). In the absence of continual fibronectin polymerization, there is a loss of fibronectin matrix fibrils, and increased levels of fibronectin degradation. Fibronectin degradation occurs intracellularly after endocytosis and can be inhibited by chloroquine, an inhibitor of lysosomal degradation, and by caveolae-disrupting agents. Down-regulation of caveolin-1 by RNAi inhibits loss of fibronectin matrix fibrils, fibronectin internalization, and fibronectin degradation; these processes can be restored by reexpression of caveolin-1. These data show that fibronectin matrix turnover occurs through a caveolin-1-dependent process. Caveolin-1 regulation of fibronectin matrix turnover is a novel mechanism regulating extracellular matrix remodeling.
Sottile
Jane
J
Center for Cardiovascular Research, Department of Medicine, University of Rochester, Rochester, NY 14642, USA. jane_sottile@urmc.rochester.edu
Chandler
Jennifer
J
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D015153:Blotting, Western; D051242:Caveolin 1; D022461:Caveolins / Q000378:metabolism*; D002460:Cell Line; D002738:Chloroquine / Q000494:pharmacology; D024042:Collagen Type I / Q000378:metabolism; D015536:Down-Regulation; D005109:Extracellular Matrix / Q000737:chemistry / Q000378:metabolism*; D005353:Fibronectins / Q000187:drug effects / Q000378:metabolism*; D016650:Fluorescein-5-isothiocyanate; D005455:Fluorescent Antibody Technique; D005456:Fluorescent Dyes; D005786:Gene Expression Regulation; D006801:Humans; D007455:Iodine / Q000378:metabolism; D018613:Microscopy, Confocal; D009130:Muscle, Smooth / Q000166:cytology* / Q000378:metabolism*; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D019700:Thrombospondin 1 / Q000378:metabolism
C495540:CAV1 protein, human; C495537:Cav1 protein, rat; D051242:Caveolin 1; D022461:Caveolins; D024042:Collagen Type I; D005353:Fibronectins; D005456:Fluorescent Dyes; D034741:RNA, Small Interfering; D019700:Thrombospondin 1; D002738:Chloroquine; D007455:Iodine; D016650:Fluorescein-5-isothiocyanate