Document Detail

Distinct structural forms of type I collagen modulate cell cycle regulatory proteins in mesangial cells.
MedLine Citation:
PMID:  10972675     Owner:  NLM     Status:  MEDLINE    
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 beta-receptors. In MCs plated on monomer type I collagen, alpha1, alpha2, and beta1 integrin chains were recruited into focal contacts. However, on polymerized type I collagen, alpha2 and beta1, but not alpha1, integrin chains were condensed into focal contacts. CONCLUSIONS: The growth-inhibitory effect of polymerized type I collagen is characterized by rapid changes of expression and/or activation of MAPK and G1-phase regulators and could result from the lack of alpha1beta1 integrin signaling in MCs on polymerized type I collagen. Conceivably, deposition of polymerized type I collagen might reflect a reparative response to control MC replication in glomerular inflammation.
H O Schöcklmann; S Lang; M Kralewski; A Hartner; A Lüdke; R B Sterzel
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Kidney international     Volume:  58     ISSN:  0085-2538     ISO Abbreviation:  Kidney Int.     Publication Date:  2000 Sep 
Date Detail:
Created Date:  2000-10-12     Completed Date:  2000-10-12     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0323470     Medline TA:  Kidney Int     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1108-20     Citation Subset:  IM; S    
Medizinische Klinik IV, Universität Erlangen-Nürnberg, Erlangen, Germany.
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MeSH Terms
Blood Proteins / pharmacology
Cell Adhesion / physiology
Cell Cycle Proteins*
Cell Nucleus / enzymology
Cells, Cultured
Collagen / chemistry,  metabolism*
Cyclin E / metabolism
Cyclin-Dependent Kinase Inhibitor p27
DNA / biosynthesis
Extracellular Matrix / enzymology
G1 Phase / drug effects,  physiology*
Glomerular Mesangium / cytology*,  enzymology*
Glomerulonephritis / metabolism,  pathology
Integrin alpha1beta1
Integrins / metabolism
Microtubule-Associated Proteins / metabolism
Mitogen-Activated Protein Kinase 1 / metabolism
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinases / metabolism
Platelet-Derived Growth Factor / pharmacology
Polymers / metabolism
Protein Kinases / metabolism
Rats, Sprague-Dawley
Receptors, Platelet-Derived Growth Factor / metabolism
S Phase / physiology
Signal Transduction / physiology
Tumor Suppressor Proteins*
Tyrosine / metabolism
Reg. No./Substance:
0/Blood Proteins; 0/Cdkn1b protein, rat; 0/Cell Cycle Proteins; 0/Cyclin E; 0/Integrin alpha1beta1; 0/Integrins; 0/Microtubule-Associated Proteins; 0/Platelet-Derived Growth Factor; 0/Polymers; 0/Tumor Suppressor Proteins; 147604-94-2/Cyclin-Dependent Kinase Inhibitor p27; 55520-40-6/Tyrosine; 9007-34-5/Collagen; 9007-49-2/DNA; EC 2.7.-/Protein Kinases; EC 2.7.1.-/histone H1 kinase; EC, Platelet-Derived Growth Factor; EC Protein Kinase 1; EC Protein Kinase 3; EC Protein Kinases

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