Changes in cell shape correlate with collagenase gene expression in rabbit synovial fibroblasts.

Abstract

Induction of the neutral proteinase, collagenase, is a marker for a specific switch in gene expression observed in rabbit synovial fibroblasts . A variety of agents, including 12-0-tetradecanoylphorbol-13-acetate, cytochalasins B and D, trypsin, chymotrypsin, poly(2-hydroxyethylmethacrylate), and trifluoperazine induced this change in gene expression . Induction of collagenase by these agents was always correlated with a marked alteration in cell morphology, although the cells remained adherent to the culture dishes . The amount of collagenase induced was positively correlated with the degree of shape change produced by a given concentration and, to some extent, with the duration of treatment . Altered cell morphology was required only during the first few hours of treatment with inducing agents ; after this time collagenase synthesis continued for up to 6 d even when agents were removed and normal flattened cell morphology was regained. All agents that altered cell morphology also produced a characteristic switch in protein secretion phenotype, characterized by the induction of procollagenase (M r 53,000 and 57,000) and a neutral metalloproteinase (M r 51,000), which accounted for approximately 25% and 15% of the protein secreted, respectively . Secretion of another neutral proteinase, plasminogen activator, did not correlate with increased collagenase secretion . In contrast, synthesis and secretion of a number of other polypeptides, including the extracellular matrix proteins, collagen and fibronectin, were concomitantly decreased . That changes in cell shape correlated with a program of gene expression manifested by both degradation and synthesis of extracellular macromolecules may have broad implications in development, repair, and pathologic conditions. The neutral proteinase, collagenase, which specifically degrades interstitial collagens, is induced by a variety of agents, including the phorbol diester tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA)' (2, 10), cytochalasin B (CB) (23), and proteolytic enzymes (52), as well as by phagocytosis (54). We have demonstrated that TPA triggers an alteration in gene expression in rabbit synovial fibroblasts that is marked by induction of several secreted proteins, including collagenase and a wide-spectrum neutral metalloproteinase, and by reduction of the synthesis of other secreted proteins, including 'Abbrevations used in this paper.

Review of current nonsurgical management of Peyronie's disease

“…This morphogenic change resulted in an altered protein secretion phenotype, manifested by increased extracellular matrix collagenase secretion as well as decreased collagen and fibronectin synthesis and secretion. 31 Similar changes have been seen when fibroblasts have been exposed in vitro to other agents such as colchicine, tamoxifen, and interferon. Lee and Ping 32 reported in 1990 on their experiments with cultured bovine fibroblasts exposed to increasing concentrations of verapamil and nifedipine.…”

Extracellular Matrix Modulates Macrophage Functions Characteristic to Atheroma

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Latrunculin and Cytochalasin Decrease Chondrocyte Matrix Retention

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