Liliana Schäfer, Karl-Friedrich Beck, Igor Raslik, Sebastian Walpen, Daniel Mihalik, Miroslava Mičegová, Katarina Macakova, Elke Schönherr, Daniela Gabriele Seidler, Georg Varga, Roland M. Schaefer, Hans Kresse, Josef Pfeilschifter
- During glomerular inflammation mesangial cells are the major source and target of nitric oxide that pro-foundly influences proliferation, adhesion, and death of mesangial cells. The effect of nitric oxide on the mRNA expression pattern of cultured rat mesangial cells was therefore investigated by RNA-arbitrarily-primed polymerase chain reaction. Employing this approach, biglycan expression turned out to be down-regulated time- and dose-dependently either by interleukin-1beta-stimulated endogenous nitric oxide production or by direct application of the exogenous nitric oxide donor, diethylenetriamine nitric oxide. There was a corresponding decline in the rate of biglycan biosynthesis and in the steady state level of this proteoglycan. In vivo, in a model of mesangioproliferative glomerulonephritis up-regulation of inducible nitric-oxide synthase mRNA was associated with reduced expression of biglycan in isolated glomeruli. Biglycan expression could be normalized, both in vitro and in vivo, by using a specific inhibitor of the inducible nitric-oxide synthase, l-N6-(l-iminoethyl)-l-lysine dihydrochloride. Further studies showed that biglycan inhibited cell adhesion on type I collagen and fibronectin because of its binding to these substrates. More importantly, biglycan protected mesangial cells from apoptosis by decreasing caspase-3 activity, and it counteracted the proliferative effects of platelet-derived growth factor-BB. These findings indicate a signaling role of biglycan and describe a novel pathomechanism by which nitric oxide modulates the course of renal glomerular disease through regulation of biglycan expression.
MetadatenAuthor: | Liliana SchäferORCiD, Karl-Friedrich BeckGND, Igor Raslik, Sebastian WalpenGND, Daniel MihalikORCiD, Miroslava MičegováORCiDGND, Katarina Macakova, Elke Schönherr, Daniela Gabriele SeidlerGND, Georg VargaGND, Roland M. SchaeferGND, Hans KresseGND, Josef PfeilschifterGND |
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URN: | urn:nbn:de:hebis:30:3-760748 |
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DOI: | https://doi.org/10.1074/jbc.M210574200 |
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ISSN: | 0021-9258 |
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Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/12719420 |
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Parent Title (English): | Journal of biological chemistry |
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Publisher: | American Society for Biochemistry and Molecular Biology Publications |
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Place of publication: | Bethesda, Md |
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Document Type: | Article |
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Language: | English |
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Date of Publication (online): | 2021/01/04 |
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Year of first Publication: | 2003 |
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Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
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Release Date: | 2024/04/25 |
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Volume: | 278.2003 |
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Issue: | 28 |
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Page Number: | 11 |
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First Page: | 26227 |
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Last Page: | 26237 |
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Institutes: | Medizin |
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| Fachübergreifende Einrichtungen / Zentrum für Arzneimittelforschung, Entwicklung und Sicherheit (ZAFES) |
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Dewey Decimal Classification: | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
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| 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
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Sammlungen: | Universitätspublikationen |
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Licence (German): | Creative Commons - CC BY - Namensnennung 4.0 International |
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