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Glomerular mesangial cells (MC) play a central role in the synthesis and turnover of the glomerular extracellular matrix. Prior studies [Davies, Thomas, Martin and Lovett (1988) Biochem. J. 251, 419-425; Martin, Davies, Thomas and Lovett (1989) Kidney Int. 36, 790-801] have characterized at the protein level a 72 kDa type IV collagenase that is secreted by cultured human and rat MC. While exposure of most cell types to interleukin-1 beta (IL-1 beta), tumour necrosis factor-alpha (TNF-alpha) or phorbol ester has little or even an inhibitory effect on 72 kDa type IV collagenase secretion, these factors significantly increased the synthesis of this enzyme by rat MC. Given this divergent pattern of expression, a homology-based PCR cloning strategy using rat MC cDNA templates was employed to define at the molecular level the structure of the mesangial 72 kDa type IV collagenase. The nucleotide sequence within the open reading frame of the rat mesangial 72 kDa type IV collagenase cDNA diverges from the sequence of the human homologue by approx. 9%. The divergence in the 3' untranslated region was much more extensive. Steady-state levels of the 3.1 kb transcript of the 72 kDa type IV collagenase were low or undetectable in resting MC, but were greatly stimulated following incubation with IL-beta, TNF-alpha or phorbol ester. None of these factors induced synthesis by MC of the closely related 92 kDa type IV collagenase. Synthesis by MC of the 72 kDa type IV collagenase was also induced by second-messenger analogues, including 8-bromo-cyclic AMP and forskolin. It is concluded that MC regulate the expression of this enzyme in an unusual, tissue-specific fashion. Cytokine and second-messenger inducibility may contribute to the enhanced expression of the enzyme during glomerular inflammatory disorders.
H P Marti, and
L McNeil, and
M Davies, and
J Martin, and
D H Lovett
April 1992,
The Journal of biological chemistry,
H P Marti, and
L McNeil, and
M Davies, and
J Martin, and
D H Lovett
July 1994,
Clinical & experimental metastasis,
H P Marti, and
L McNeil, and
M Davies, and
J Martin, and
D H Lovett
October 1995,
Developmental biology,
H P Marti, and
L McNeil, and
M Davies, and
J Martin, and
D H Lovett
January 1994,
The American journal of pathology,
H P Marti, and
L McNeil, and
M Davies, and
J Martin, and
D H Lovett
January 1994,
International journal of cancer,
H P Marti, and
L McNeil, and
M Davies, and
J Martin, and
D H Lovett
March 1997,
Journal of the American Society of Nephrology : JASN,
H P Marti, and
L McNeil, and
M Davies, and
J Martin, and
D H Lovett
March 1994,
The Biochemical journal,
H P Marti, and
L McNeil, and
M Davies, and
J Martin, and
D H Lovett
April 1997,
Proceedings of the National Academy of Sciences of the United States of America,
H P Marti, and
L McNeil, and
M Davies, and
J Martin, and
D H Lovett
March 1996,
FEBS letters,
H P Marti, and
L McNeil, and
M Davies, and
J Martin, and
D H Lovett
March 1991,
Diabetologia,
