mRNA Expression of Podocyte Associated Proteins in Peripheral Blood Mononuclear Cells of Type 2 Diabetes Mellitus Patients with and without Nephropathy

Abstract

Background: Diabetic nephropathy is the leading cause of End-Stage Renal Disease (ESRD) emerging in developed as well as developing countries, with the complicated pathogenesis. The study of expression of the genes related to kidney cells e.g. podocytes has been shown to be associated with the condition, helping in the elucidation of pathogenesis of the disease. Previously the gene expression associated was studied in urine samples. Material and Methods: In the present study, it was attempted to analyze the mRNA expression of podocyte related genes viz. podocalyxin, podocin and synaptopodin in Peripheral Blood Mononuclear Cells (PBMCs) in patients with diabetes with and without nephropathy in comparison with healthy controls by reverse transcriptase Polymerase Chain Reaction (PCR), followed by semi-quantitative PCR. Results: The expression of Synaptopodin (SYNPO) was increased in diabetics than the controls, while no significant difference was found for Podocalixyn (PODXL) and Podocin (NPHS2). The expression of PODXL and NPHS2 was significantly up-regulated; SYNPO was unaltered in microalbuminuric patients than healthy controls. PODXL and SYNPO were increased significantly in nephropathy subjects than controls, with no significant change in NPHS2. The expression of only PODXL was found to be upregulated in microalbuminuric patients as compared to T2DM patients without nephropathy. PODXL, SYNPO were significantly up-regulated and NPHS2 was significantly down-regulated in nephropathy subjects as compared to T2DM patients without nephropathy. A significant down-regulation was found for NPHS2 expression in nephropathy patients than microalbuminuric patients of T2DM with nephropathy. Conclusion: The detection of gene expression of these proteins can be used as an early marker for the detection of development of nephropathy in T2DM patients and preventive measures can be taken to prolong the onset of nephropathy in these patients, increasing the life expectancy.

Keywords

• diabetic nephropathy
• podocytes
• synaptopodin
• podocalixyn
• podocin
• gene expression