Abstract
Type IV collagen, which is encoded by six genetically distinct α-chains (α1-α6), is a major component of the kidney glomerulus. The α1(IV) and α2(IV) chains are present predominantly in the mesangial matrix, whereas the α3(IV), α4(IV), and α5(IV) chains are localized almost exclusively to the glomerular basement membrane (GBM). Thickening of the GBM and expansion of the mesangial matrix are believed to contribute to the pathogenesis of diabetic nephropathy. In the present study, we evaluated the expression of α1(IV), α3(IV), and α5(IV) chains in rat glomerular endothelial (GEndC) and mesangial cells (GMC). Under physiological concentrations of glucose (5 mM), α1(IV) and α5(IV) chains were detectable in GMCs, with an obvious absence of α3(IV) chain. All three isoforms tested were present in GEndCs. At diabetic concentrations of glucose (25 mM), α1(IV) was up-regulated in GMCs, whereas expression level of α1(IV) remained unaltered in GEndCs. The α3(IV) and α5(IV) chains were up-regulated in GEndCs, but remained unchanged in GMCs under diabetic glucose concentrations (25 mM). Collectively, our results demonstrate that GMC might contribute to mesangial matrix expansion, mediated by α1(IV) collagen, while GEndC might contribute to thickening of GBM, mediated by α3(IV) collagen, in patients with diabetic nephropathy.
Original language | English (US) |
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Pages (from-to) | 401-407 |
Number of pages | 7 |
Journal | Biochemical and Biophysical Research Communications |
Volume | 295 |
Issue number | 2 |
DOIs | |
State | Published - 2002 |
Funding
This study was supported in part by Grants DK51711 and DK55001 from the NIH and a research fund from the Beth Israel Deaconess Medical Center for the Program in Matrix Biology, by grants from the Deutsche Forschungsgemeinschaft DFG ZE5231/1 to M. Zeisberg and by a grant from the Japan Research Foundation for Clinical Pharmacology to Y. Hamano. We thank Lori Siniski for her help in preparation of the manuscript.
Keywords
- Collagen isoforms
- Diabetic nephropathy
- Glomerular basement membrane
- Type IV collagen
ASJC Scopus subject areas
- Molecular Biology
- Biophysics
- Biochemistry
- Cell Biology