Abstract | OBJECTIVE: RESEARCH DESIGN AND METHODS: Diabetes was induced by STZ injections in collagen VIII-deficient or wild-type mice. Functional and histological analyses were performed 40 days after induction of diabetes. Type VIII collagen expression was assessed by Northern blots, immunohistochemistry, and real-time PCR. Proliferation of primary mesangial cells was measured by thymidine incorporation and direct cell counting. Expression of phosphorylated extracellular signal-regulated kinase (ERK1/2) and p27(Kip1) was assessed by Western blots. Finally, Col8a1 was stably overexpressed in mesangial cells. RESULTS: Diabetic wild-type mice showed a strong renal induction of type VIII collagen. Diabetic Col8a1(-)/Col8a2(-) animals revealed reduced mesangial expansion and cellularity and extracellular matrix expansion compared with the wild type. These were associated with less albuminuria. High- glucose medium as well as various cytokines induced Col8a1 in cultured mesangial cells. Col8a1(-)/Col8a2(-) mesangial cells revealed decreased proliferation, less phosphorylation of Erk1/2, and increased p27(Kip1) expression. Overexpression of Col8a1 in mesangial cells induced proliferation. CONCLUSIONS:
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Authors | Ulrike Hopfer, Helmut Hopfer, Catherine Meyer-Schwesinger, Ivonne Loeffler, Naomi Fukai, Bjorn R Olsen, Rolf A K Stahl, Gunter Wolf |
Journal | Diabetes
(Diabetes)
Vol. 58
Issue 7
Pg. 1672-81
(Jul 2009)
ISSN: 1939-327X [Electronic] United States |
PMID | 19401424
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Col8a2 protein, mouse
- Collagen Type VIII
- DNA Primers
- RNA
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Topics |
- Animals
- Cell Division
- Collagen Type VIII
(deficiency, genetics)
- DNA Primers
- Diabetes Mellitus, Experimental
(physiopathology)
- Diabetic Nephropathies
(genetics, pathology, physiopathology, prevention & control)
- Glomerular Mesangium
(pathology)
- Male
- Mice
- Mice, Knockout
- Polymerase Chain Reaction
- RNA
(genetics)
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