Abstract
A common complication of both type I and type II diabetes is nephropathy, characterized by accumulation of extracellular matrix in the glomerular mesangium. This indicates a central role of mesangial cells in the pathophysiology of diabetic nephropathy. Using the proteomic approach, it was earlier elucidated in a rat model that the proteasome subunit-α type-6 protein (PSMA6) is suppressed in the renal cortex in nephropathic kidney. However, the underlying mechanism effecting suppression of PSMA6 protein in the renal cortex is not yet known. Twenty diabetic patients were enrolled and the expression level of PSMA6 in them was detected by immunohistochemistry. The protein and mRNA expression levels of PSMA6 in NRK-52E cells under high glucose condition were determined by Western blot and quantitative real-time PCR, respectively. Dual luciferase assay was used to detect the relationship of PSMA6 and miR-4490. Our results show that PSMA6 protein is down-regulated in patients with diabetic nephropathy compared with healthy control. Using the NRK-52E cell line cultured under high glucose condition as an in vitro model of diabetic nephropathy, we show that loss of PSMA6 protein expression occured independent of changes the in PSMA6 mRNA expression. We next elucidate that PSMA6 mRNA is post-transcriptionally regulated by the microRNA (miRNA)-4490, whose expression is inversely correlated to PSMA6 protein expression. Using reporter assays we show that PSMA6 is a direct target of the miR-4490. Exogenous manipulation of miR-4490 levels modulated expression of PSMA6, indicating that miR-4490 can be tested as a biomarker for nephropathy in diabetic patients.
Highlights
A common complication of type I and type II diabetes is nephropathy, where extracellular matrix leaks into the glomerular region of the kidney [1]
A P
To investigate what regulates PSMA6 protein expression during diabetic nephropathy, we used the in vitro NRK-52E cells, which have been shown to induce diabetic nephropathy-like features inclusive of gene and protein expressions when cultured at high glucose concentrations for prolonged periods [12]
Summary
A common complication of type I and type II diabetes is nephropathy, where extracellular matrix leaks into the glomerular region of the kidney [1]. This microvascular disorder occurs in 25–40% of all diabetic patients and is the biggest cause of both end stage renal disease (ESRD) and diabetic mortality [2]. Using a rat model of diabetic nephropathy it was observed that expression of proteasome subunit-α type-6 protein (PSMA6) is suppressed in renal cortex of nephropathic kidney [9]. Regulatory mechanisms underlying PSMA6 protein expression in diabetic nephropathy are not completely defined
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
