Shweta Bansal

Personal Information
Title Assistant Professor
Expertise Nephropathy
Institution University of Texas HSC San Antonio
Data Summary
Grants/SubContracts 1
Progress Reports 1
Publications 2
Protocols 0
Committees 2


Role of NGAL in Regulation of FGF23 in Diabetic Kidney Disease
Diabetes is the most common cause of chronic kidney diseae (CKD) in the United States and CKD patients carry double the risk of stroke, cornoary heart disease and death compared to patients with diabetes alone. The classical risk factors do not fully account for increased risk of cardiovascular (CV) disease in these patients. Lately, phoshaturic hormone fibroblast growth factor-23 (FGF23) and acute phase reactant neutrophil gelatinase-associated lipocalin (NGAL) have been associated with increased CV disease and mortality in CKD as well as general population. Both of these proteins rise with progressive worsening of kidney function. However, till date their regulation in CKD and mechanisms of association with worse outcome are not well understood. We reported recently that circulating NGAL associates strongly with FGF23 in humans with diabetes and diabetic nephropathy, independent of renal function, calcium, phosphorus and CRP. In addition, we found that NGAL stimulated production of FGF23 in cultured mouse osteocytes, suggesting a direct regulatory action of NGAL on FGF23. The implications of this observation, if confirmed in prospective clinical and mechanistic studies, may be far reaching by demonstrating a central role of the acute phase reactant NGAL, and possibly of inflammation, in FGF23 regulation. We hypothesize that the blood levels of NGAL are highly correlated with FGF23 in diabetic nephropathy patients; this association is result of stimulatory action of NGAL on the osteocytic synthesis and secretion of FGF23 via a mechanism that is direct and not affected by other acute phase reactants or inflammatory cytokines. We will test this hypothesis with two parallel and tightly related lines of investigations. In Aim 1, we assess the relationship between NGAL and FGF23 while controlling for all the confounding factors known to affect their regulation, in a clinical sub-study that will utilize a population of 110 diabetic nephropathy patients recruited for another ongoing prospective trial (parent study). This population is well characterized for their dietary intake, measured renal function, systemic redox balance, and nutritonal status. For the sub-study, patients will receive additional analysis of circulating FGF23 and NGAL, parametes of bone mineral and iron metabolism and systemic inflammation. In Aim 2, we investigate the effect and mechanism of action of NGAL on FGF23 production in vitro studies. Mouse osteocytes will be treated with NGAL or inflammatory cytokines or serum from diabetic nephropathy patients or healthy controls in different combinations to tease out the independent effect of NGAL on FGF23 synthesis. Validation of the above hypothesis will establish NGAL as the stimulus of FGF23 synthesis in diabetic nephropathy patients and provides foundation to explore role of molecular inhibitors of NGAL as a means for reducing FGF23 levels and for decreasing the rate of progression of kidney and cardiovascular disease and mortality in these patients with diabetic nephropathy.

Progress Reports
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Role of NGAL in Regulation of FGF23 in Diabetic Kidney Disease (Bansal, Shweta)
10/28/2014View Progress Report Document

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