Regulation of fibronectin matrix deposition and cell proliferation by the PINCH-ILK-CH-ILKBP complex

FASEB J. 2002 Aug;16(10):1298-300. doi: 10.1096/fj.02-0089fje. Epub 2002 Jun 7.

Abstract

Alteration in renal glomerular mesangial cell growth and fibronectin matrix deposition is a hallmark of glomerulosclerosis, which ultimately leads to end-stage renal failure. We have previously shown that the expression of integrin-linked kinase (ILK), a cytoplasmic component of the cell-extracellular matrix contacts, is increased in mesangial cells in human patients with diabetic nephropathy. We show here that ILK forms a complex with PINCH and CH-ILKBP in primary mesangial cells, which are co-clustered at fibrillar adhesions, sites that are involved in fibronectin matrix deposition. To investigate functional significance of the PINCH-ILK-CH-ILKBP complex formation, we expressed the PINCH-binding N-terminal fragment and the CH-ILKBP-binding C-terminal fragment of ILK, respectively, in mesangial cells by using an adenoviral expression system. Overexpression of either the N-terminal fragment or the C-terminal fragment of ILK effectively inhibited the PINCH-ILK-CH-ILKBP complex formation. Inhibition of the PINCH-ILK-CH-ILKBP complex formation significantly reduced fibronectin matrix deposition and inhibited cell proliferation. These results indicate that the PINCH-ILK-CH-ILKBP complex is critically involved in the regulation of mesangial fibronectin matrix deposition and cell proliferation, and suggest that it may potentially serve as a useful target in the therapeutic control of progressive renal failure and other pathological processes involving abnormal cell proliferation and fibronectin matrix deposition.

MeSH terms

  • Actinin*
  • Animals
  • Carrier Proteins / analysis
  • Carrier Proteins / metabolism*
  • Cell Adhesion
  • Cell Division
  • Cells, Cultured
  • DNA-Binding Proteins / analysis
  • DNA-Binding Proteins / metabolism*
  • Extracellular Matrix / metabolism
  • Fibronectins / metabolism*
  • Glomerular Mesangium / cytology
  • Glomerular Mesangium / metabolism*
  • Glomerular Mesangium / physiology
  • Macromolecular Substances
  • Microfilament Proteins
  • Models, Biological
  • Peptide Fragments / genetics
  • Protein-Serine-Threonine Kinases / analysis
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • Rats
  • Transfection

Substances

  • Carrier Proteins
  • DNA-Binding Proteins
  • Fibronectins
  • Macromolecular Substances
  • Microfilament Proteins
  • PARVA protein, human
  • PARVB protein, human
  • Peptide Fragments
  • Actinin
  • integrin-linked kinase
  • Protein-Serine-Threonine Kinases