Dissociated expression of collagen type IV subchains in diabetic kidneys of KKAy mice

Diabetic nephropathy is characterized by thickening of the glomerular basement membrane and expansion of the mesangial matrix. The glomerular basement membrane is assembled from at least five genetically distinct collagen IV chains. In patients with diabetic nephropathy, differential distribution of these components has been demonstrated. In order to clarify the relationship between progression of diabetic nephropathy and altered type IV collagen assembly in the renal cortex, we examined steady state mRNA levels encoding collagen IV subchains in the kidney cortices of spontaneously diabetic KKAy mice and nondiabetic C57black mice as controls. They were sacrificed at 4, 8, 16, and 24 weeks of age. Northern and dot blot analyses were performed using 32P-labeled mouse probes for classical alpha1(IV) and alpha2(IV) and for alpha3(IV), alpha4(IV), and alpha5(IV) minor chains. The mRNA levels for all collagen IV chains peaked at 4 weeks of age and declined rapidly thereafter in the nondiabetic mice. At all times, alpha1(IV) and alpha2(IV) mRNA expressions were abundant and almost unchanged in KKAy mice. In contrast, mRNA levels for alpha3(IV), alpha4(IV), and alpha5(IV) progressively changed with age. It appears that the expression of minor collagen IV chains is dissociated from the alpha1(IV) and alpha2(IV) chains in diabetic nephropathy. Moreover, an unbalanced increase in the production may affect collagen IV assembly and contribute to basement membrane thickening in diabetic nephropathy of KKAy mice.