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Up‐regulation of tissue inhibitor of metalloproteinases‐3 gene expression by TGF‐β in articular chondrocytes is mediated by serine/threonine and tyrosine kinases

Up‐regulation of tissue inhibitor of metalloproteinases‐3 gene expression by TGF‐β in articular... The balance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) regulates extracellular matrix turn‐over in normal animal development, cancer cell metastasis, atherosclerotic plaque rupture and erosion of arthritic cartilage. Transforming growth factor beta (TGF‐β), an inducer of matrix synthesis, potently enhances mRNA and protein of a recently characterized MMP inhibitor, TIMP‐3, in bovine articular chondrocytes. We examined the implication of protein kinases in the TGF‐β‐mediated induction of TIMP‐3 expression by utilizing activators and inhibitors of these enzymes. Protein kinase A activators, dibutyryl cyclic AMP, or forskolin had little or no effect, respectively, while phorbol 12‐myristate 13‐acetate (PMA), a PKC activator, increased TIMP‐3 gene expression. H7, a serine/threonine protein kinase inhibitor, markedly reduced the response of TIMP‐3 gene to TGF‐β. Furthermore, two protein tyrosine kinase inhibitors, genistein and herbimycin A, inhibited TGF‐β induction of TIMP‐3. H7 and genistein also suppressed TGF‐β‐induced TIMP‐3 protein expression. These results suggest that TGF‐β signaling for TIMP‐3 gene induction involves H7‐sensitive serine/threonine kinase as well as herbimycin A‐ and genistein‐sensitive protein tyrosine kinases. J. Cell. Biochem. 70:517–527, 1998. © 1998 Wiley‐Liss, Inc. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Cellular Biochemistry Wiley

Up‐regulation of tissue inhibitor of metalloproteinases‐3 gene expression by TGF‐β in articular chondrocytes is mediated by serine/threonine and tyrosine kinases

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References (50)

Publisher
Wiley
Copyright
Copyright © 1998 Wiley Subscription Services, Inc., A Wiley Company
ISSN
0730-2312
eISSN
1097-4644
DOI
10.1002/(SICI)1097-4644(19980915)70:4<517::AID-JCB8>3.0.CO;2-M
Publisher site
See Article on Publisher Site

Abstract

The balance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) regulates extracellular matrix turn‐over in normal animal development, cancer cell metastasis, atherosclerotic plaque rupture and erosion of arthritic cartilage. Transforming growth factor beta (TGF‐β), an inducer of matrix synthesis, potently enhances mRNA and protein of a recently characterized MMP inhibitor, TIMP‐3, in bovine articular chondrocytes. We examined the implication of protein kinases in the TGF‐β‐mediated induction of TIMP‐3 expression by utilizing activators and inhibitors of these enzymes. Protein kinase A activators, dibutyryl cyclic AMP, or forskolin had little or no effect, respectively, while phorbol 12‐myristate 13‐acetate (PMA), a PKC activator, increased TIMP‐3 gene expression. H7, a serine/threonine protein kinase inhibitor, markedly reduced the response of TIMP‐3 gene to TGF‐β. Furthermore, two protein tyrosine kinase inhibitors, genistein and herbimycin A, inhibited TGF‐β induction of TIMP‐3. H7 and genistein also suppressed TGF‐β‐induced TIMP‐3 protein expression. These results suggest that TGF‐β signaling for TIMP‐3 gene induction involves H7‐sensitive serine/threonine kinase as well as herbimycin A‐ and genistein‐sensitive protein tyrosine kinases. J. Cell. Biochem. 70:517–527, 1998. © 1998 Wiley‐Liss, Inc.

Journal

Journal of Cellular Biochemistry – Wiley

Published: Mar 15, 1999

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