| Distinct structural forms of type I collagen modulate cell cycle regulatory proteins in mesangial cells. | |
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MedLine Citation:
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PMID: 10972675 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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H O Schöcklmann; S Lang; M Kralewski; A Hartner; A Lüdke; R B Sterzel |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Kidney international Volume: 58 ISSN: 0085-2538 ISO Abbreviation: Kidney Int. Publication Date: 2000 Sep |
Date Detail:
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Created Date: 2000-10-12 Completed Date: 2000-10-12 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 0323470 Medline TA: Kidney Int Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 1108-20 Citation Subset: IM; S |
Affiliation:
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Medizinische Klinik IV, Universität Erlangen-Nürnberg, Erlangen, Germany. Harald.Schoecklmann@t-online.de |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals 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 Hyperplasia Integrin alpha1beta1 Integrins / metabolism Male Microtubule-Associated Proteins / metabolism Mitogen-Activated Protein Kinase 1 / metabolism Mitogen-Activated Protein Kinase 3 Mitogen-Activated Protein Kinases / metabolism Phosphorylation Platelet-Derived Growth Factor / pharmacology Polymers / metabolism Protein Kinases / metabolism Rats Rats, Sprague-Dawley Receptors, Platelet-Derived Growth Factor / metabolism S Phase / physiology Signal Transduction / physiology Tumor Suppressor Proteins* Tyrosine / metabolism |
| Chemical | |
Reg. No./Substance:
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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 2.7.10.1/Receptors, Platelet-Derived Growth Factor; EC 2.7.11.24/Mitogen-Activated Protein Kinase 1; EC 2.7.11.24/Mitogen-Activated Protein Kinase 3; EC 2.7.11.24/Mitogen-Activated Protein Kinases |
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