Changes in cell shape correlate with collagenase gene expression in rabbit synovial fibroblasts
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-O-tetradecanolyphorbol-13-acetate, cytochalasins B and D, trypsin, chymotrypsin, poly(2-hydroxyethylmethacrylate), and trifluorperazine 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/sub r/ 53,000 and 57,000) and a neutral metalloproteinase (M/sub 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. 56 references, 8 figures, 4 tables.
- Research Organization:
- Univ. of California, San Francisco, CA (United States)
- DOE Contract Number:
- AC03-76SF01012
- OSTI ID:
- 5808893
- Journal Information:
- J. Cell Biol.; (United States), Vol. 98:5
- Country of Publication:
- United States
- Language:
- English
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FIBROBLASTS
MORPHOLOGICAL CHANGES
HYDROXY COMPOUNDS
BIOLOGICAL EFFECTS
PEPTIDE HYDROLASES
ENZYME ACTIVITY
PHENOTHIAZINES
PHORBOL ESTERS
TRYPSIN
GENES
RABBITS
ANIMAL CELLS
ANIMALS
AZINES
CARCINOGENS
CONNECTIVE TISSUE CELLS
ENZYMES
ESTERS
HETEROCYCLIC COMPOUNDS
HYDROLASES
MAMMALS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
SERINE PROTEINASES
SOMATIC CELLS
VERTEBRATES
550300* - Cytology