Abstract
Osteopontin (OPN) is one of the proinflammatory cytokines upregulated in the kidneys of diabetic animals and patients with diabetic nephropathy (DN). An increase in albuminuria and albumin‐bound fatty acids presents a proinflammatory environment to the proximal tubules in proteinuric kidney diseases including DN. This study was designed to examine if fatty acid overload or albumin itself could stimulate OPN production by renal tubular epithelial cells. Renal tubular OPN expression and secretion were examined in Zucker diabetic (ZD) rats and NRK‐52E cell line exposure to bovine serum albumin (BSA) or BSA overloaded with saturated fatty acid palmitate. Gene microarray and real‐time PCR confirmed an albuminuria‐associated upregulation of OPN transcripts in kidney cortex of ZD rats at the age of 7–20 weeks. Immunofluorescence staining of kidney sections revealed an increase in OPN protein in damaged proximal tubules of diabetic rats. Western blot analysis detected a progressive increase in urinary OPN levels in the ZD rats, which was prevented by antiproteinuric treatment with losartan, an angiotensin II receptor blocker. When exposed to fatty acid‐free bovine serum albumin (BSA, 10 mg/ml), NRK‐52E cells exhibited an increase in OPN protein expression. Palmitate (250 μM) further enhanced albumin‐induced OPN in NRK‐52E cells. These results demonstrate a stimulatory effect of albumin and its conjugated fatty acids on OPN expression in renal tubule epithelial cells. Thus, besides lowering albuminuria/proteinuria, mitigating circulating fatty acid levels may be an important factor in preventing renal inflammation in proteinuric diseases.Support or Funding InformationNIH SC1DK112151, NIH/NCRR/RCMI 8G12MD007602 & 8U54MD007588This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
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