Relationships of cell proliferation and expression of integrin subunits and type I collagen in skin fibroblasts with renal lesions in patients with IDDM.

Previous studies have shown that cultured skin fibroblasts (SFs) from insulin-dependent diabetic mellitus (IDDM) patients with diabetic nephropathy (DN) exhibit both increased proliferation and Na+/H+ antiporter activity. The present study correlated the growth rate and mRNA expression of integrin subunits, extracellular matrix molecules, and transforming growth factor-beta in cultured SFs, with the biopsy determined rate of development of DN lesions ranging from slow to rapid in nine IDDM patients. These varying rates of development of DN lesions were expressed by a mesangial expansion score as estimated by the rate of change in mesangial fraction volume per year. Cultured SF proliferation by direct cell counts positively correlated with mesangial expansion score (r = 0.65; P < 0.05). Expression of cultured SF alpha3 integrin subunit mRNA levels, as well as type I collagen mRNA (P < 0.05 for both), but not transforming growth factor-beta mRNA levels (Northern blot analysis), were also positively correlated with mesangial expansion score. We postulate that these observations of correlations between activities of cultured SFs and the rate of progression of DN lesions may be predictive of the risk to develop clinical DN in IDDM, may be in part genetically regulated, and may be of pathogenetic importance.