|Distinct structural forms of type I collagen modulate cell cycle regulatory proteins in mesangial cells.|
|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|
Related Documents :
|16428445 - Glycogen synthase kinase 3 and h-prune regulate cell migration by modulating focal adhe...
11035755 - Involvement of focal adhesion kinase in escherichia coli invasion of human brain microv...
17697885 - Analysis of integrin signaling by fluorescence resonance energy transfer.
18292945 - Laminin-1-derived scrambled peptide ag73t disaggregates laminin-1-induced ovarian cance...
14570565 - Regulation of map kinase signaling modules by scaffold proteins in mammals.
22315395 - Insulin and ampk regulate fa translocase/cd36 plasma membrane recruitment in cardiomyoc...
|Type: Journal Article; Research Support, Non-U.S. Gov't|
|Title: Kidney international Volume: 58 ISSN: 0085-2538 ISO Abbreviation: Kidney Int. Publication Date: 2000 Sep|
|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|
|Languages: eng Pagination: 1108-20 Citation Subset: IM; S|
|Medizinische Klinik IV, Universität Erlangen-Nürnberg, Erlangen, Germany. Harald.Schoecklmann@t-online.de|
|APA/MLA Format Download EndNote Download BibTex|
Blood Proteins / pharmacology
Cell Adhesion / physiology
Cell Cycle Proteins*
Cell Nucleus / enzymology
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
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
Receptors, Platelet-Derived Growth Factor / metabolism
S Phase / physiology
Signal Transduction / physiology
Tumor Suppressor Proteins*
Tyrosine / metabolism
|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 184.108.40.206/Receptors, Platelet-Derived Growth Factor; EC 220.127.116.11/Mitogen-Activated Protein Kinase 1; EC 18.104.22.168/Mitogen-Activated Protein Kinase 3; EC 22.214.171.124/Mitogen-Activated Protein Kinases|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Inhibition of heparin-binding epidermal growth factor-like growth factor increases albuminuria in pu...
Next Document: Antibodies to both ICAM-1 and LFA-1 do not protect the kidney against toxic (HgCl2) injury.