Osteopontin plays a critical role in interstitial fibrosis but not glomerular sclerosis in diabetic nephropathy.

OBJECTIVE

Osteopontin (OPN) has been implicated in the pathology of several renal conditions. The aim of this study was to clarify the roles of OPN in diabetic nephropathy.

METHODS

Diabetes mellitus (DM) was induced in wild-type (WT) and OPN knockout (KO) mice by injecting streptozotocin. The mice were killed 20 weeks after induction of DM and their kidneys removed.

RESULTS

Renal mRNA expression of OPN was increased in WT-DM mice compared to WT-sham mice. Immunohistochemistry showed high levels of OPN expression in the proximal tubules of WT-DM mice. Kidney weight and urinary albumin excretion increased to similar levels in the WT-DM and KO-DM mice. Interstitial fibrosis was increased in WT-DM mice compared to KO-DM mice. However, there were no differences in the degree of mesangial expansion or glomerular hypertrophy between the two groups. F4/80-positive cells (macrophages) and FSP-1-positive cells (fibroblasts) showed significantly higher infiltration in WT-DM mice than in KO-DM mice. Renal mRNA expression of NADPH oxidase subunits and urinary 8-isoprostane excretion were also increased in WT-DM mice.

CONCLUSIONS

These results indicated that OPN is a key molecule that induces interstitial fibrosis in the diabetic kidney, but does not induce glomerular sclerosis.