Fatty acid binding protein 3 as a potential mediator for diabetic nephropathy in eNOS deficient mouse

https://doi.org/10.1016/j.bbrc.2014.10.121Get rights and content
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Highlights

  • Among the FABP family, FABP3 is the most significantly induced in the glomerular injury of diabetic eNOS knockout mice.

  • FABP3 is dominantly induced in the mesangial cells in the diabetic glomerular injury.

  • FABP3 expression is associated with inflammatory response in the glomerulus.

  • FABP3 enhances MCP-1 expression in response to fatty acid in the cultured mesangial cells.

Abstract

In human diabetic nephropathy, glomerular injury was found to comprise lipid droplets, suggesting that abnormal lipid metabolism might take place in the development of diabetic glomerular injury. However, its precise mechanism remains unclear. Fatty acid binding protein (FABP) is currently considered as a key molecule for lipid metabolism. Since diabetic eNOS knockout (KO) mouse is considered to be a good model for human diabetic nephropathy, we here investigated whether FABP could mediate glomerular injury in this model. We found that glomerular injuries were associated with inflammatory processes, such as macrophage infiltration and MCP-1 induction. Microarray assay with isolated glomeruli revealed that among 10 isoforms in FABP family, FABP3 mRNA was most highly expressed in diabetic eNOSKO mice compared to non-diabetic eNOSKO mice. FABP3 protein was found to be located in the mesangial cells. Overexpression of FABP3 resulted in a greater response to palmitate, a satulated FA, to induce MCP-1 in the rat mesangial cells. In turn, the heart, a major organ for FABP3 protein in normal condition, failed to alter its expression level under diabetic condition in either wild type or eNOSKO mice. In conclusion, FABP3 is induced in the mesangial cells and likely a mediator to induce MCP-1 in the diabetic nephropathy.

Keywords

Fatty acid
Endothelial
Inflammation
Nitric oxide
Advanced diabetic nephropathy
FABP

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