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Distinct structural forms of type I collagen modulate cell cycle regulatory proteins in mesangial cells.
Distinct structural forms of type I collagen modulate cell cycle regulatory proteins in mesangial cells.
- Source :
-
Kidney International . Sep2000, Vol. 58 Issue 3, p1108-1120. 13p. 3 Black and White Photographs, 5 Diagrams, 4 Graphs. - Publication Year :
- 2000
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Abstract
- Distinct structural forms of type I collagen modulate cell cycle regulatory proteins in mesangial cells. Background. Extracellular matrix molecules profoundly regulate cell behavior, including proliferation. In glomerulonephritis, type I collagen accumulates in the mesangium and is constantly structurally modified and degraded during the course of the disease. Methods. We studied how two structurally distinct forms of type I collagen, monomer versus polymerized fibrils, affect cell proliferation, mitogen-activated protein kinase (MAPK) activation, and expression of G1-phase regulatory proteins in cultured rat mesangial cells (MCs). To analyze the possible involvement of collagen-binding integrins in type I collagen-derived growth signals further, distribution patterns of integrin chains were examined by immunocytochemistry. Results. Polymerized type I collagen completely prevented the increase of DNA synthesis and cell replication induced by 5% fetal calf serum (FCS) or 25 ng/mL platelet-derived growth factor (PDGF) in MCs on monomer type I collagen. Protein expression of cyclins D1 and E was markedly down-regulated in MCs plated on polymerized type I collagen for eight hours in 5% FCS, as compared with MCs on monomer type I collagen. Incubation with 5% FCS reduced expression of the cdk-inhibitor protein p27Kip1 on monomer but not on polymerized type I collagen. Moreover, polymerized type I collagen markedly reduced cyclin E-associated kinase activity in the presence of 5% FCS. Polymerized type I collagen diminished the PDGF-induced phosphorylation and nuclear translocation of p42/p44 MAPK, but did not affect phosphorylation of PDGF β-receptors. In MCs plated on monomer type I collagen, α1, α2, and β1 integrin chains were recruited into focal contacts. However, on polymerized type I collagen, α2 and β1, but not α1, integrin chains were... [ABSTRACT FROM AUTHOR]
- Subjects :
- *COLLAGEN
*CELL cycle
*HYPERPLASIA
Subjects
Details
- Language :
- English
- ISSN :
- 00852538
- Volume :
- 58
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- Kidney International
- Publication Type :
- Academic Journal
- Accession number :
- 5881798