Differential expression of type IV collagen isoforms in rat glomerular endothelial and mesangial cells

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.