Fibronectin dependent upregulation of matrix metalloproteinases in hepatic stellate cells.
Activation and transition of hepatic stellate cells (HSCs) to myofibroblast (MFB)-like cells is influenced by growth factors, cytokines and matrix proteins like fibronectin (FN). To examine whether the FN-dependent transition of HSCs is mediated through FN receptor, a marker function, such as matrix metallo-proteinase (MMP) production by HSCs in primary culture was studied. An upregulation of MMP production by HSCs maintained on FN was observed. FN-dependent upregulation of MMPs was significantly reduced when cells were pre-treated with antibodies to alpha5beta1 integrin. Treatment of cells with genistein, a protein kinase C inhibitor completely blocked the gelatinase production by HSCs, indicating that the FN-dependent upregulation of MMPs is mediated through integrins and it involves tyrosine phosphorylation dependent signaling pathways.
Department of Biochemistry, University of Kerala,Karyavattom, Trivandrum 695 581, India.
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Pranitha
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Sudhakaran
D000818:Animals; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism*; D055166:Hepatic Stellate Cells / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D016023:Integrins / Q000276:immunology / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000096:biosynthesis / Q000378:metabolism*; D051381:Rats; D015854:Up-Regulation
D024042:Collagen Type I; D005353:Fibronectins; D016023:Integrins; D020782:Matrix Metalloproteinases