Evaluation of Renal Gene Expression of Protein Kinase C (PKC) Isoforms in Diabetic and Nondiabetic Proliferative Glomerular Diseases

The protein kinase C (PKC) family consists of 13 members categorized as conventional or novel depending on whether diacylglycerol, calcium, or phosphatidylserine is required for activation. High glucose leads to activation of different forms of PKC across tissue types, thus determining the kind of diabetes-induced organ damage. PKC beta was reported to have a positive role in B-lymphocyte activity through activation of NF-kappa B, leading to various immune disorders. We examined renal expression of two PKC isoforms alpha and beta in renal biopsies of patients with diabetic nephropathy, lupus nephritis (LN) (Class 3-4), and mesangioproliferative glomerulonephritis (MPGN) to explore the role of each isoform in different glomerular diseases. PKC alpha and beta gene expression was studied by quantitative real-time reverse transcription-PCR in 20 patients with type 2 diabetes and proteinuria (serum creatinine 2.04 +/- 0.85 mg/dl, 24-h urinary protein 3.61 +/- 1.75 g, eGFR 37.85 +/- 17.89 ml/min/1.73 m(2)), 20 patients with proliferative LN (serum creatinine 1.67 +/- 1.50 mg/dl, 24-h urinary protein 4.46 +/- 5.01 g, eGFR 69.62 +/- 40.93 ml/min/1.73 m(2)), and 20 patients with MPGN (serum creatinine 3.32 +/- 2.79 mg/dl, 24-h urinary protein 4.65 +/- 4.11 g, eGFR 32.62 +/- 29.56 ml/min/1.73 m(2)). Normal tissues from the normal pole of four kidneys removed because of renal tumor served as controls. PKC alpha gene expression was significantly increased in diabetic kidneys compared to LN and MPGN (316.95 +/- 152.94 mu g/ml vs. 185.97 +/- 32.13 and 195.46 +/- 46.45 mu g/ml, p < 0.05). PKC beta gene expression was significantly increased in the LN and MPGN groups compared to the diabetic nephropathy group (41.01 +/- 14.03 and 39.93 +/- 16.41 mu g/ml, respectively, vs. 18.20 +/- 4.91 mu g/ml, p < 0.05). Significant correlation was noted between the PKC mu gene concentrations and proteinuria in diabetic patients. Renal expression of PKC alpha and beta genes in control tissues were significantly lower compared to diabetic kidneys, LN, and MPGN groups (32.31 +/- 0.36 and 4.67 +/- 2.41 mu g/ml, respectively, p < 0.001). The study revealed enhanced renal gene expression of both PKC isoforms alpha and beta in diabetic kidney tissues, LN, and MPGN, but in different patterns. PKC alpha gene expression was significantly increased in diabetic patients with chronic kidney disease. The increased expression of the PKC alpha gene in LN and MPGN highlights its role in regulation of the immune system. This may represent potential therapeutic targets for prevention of progressive kidney injury in diabetic and proliferative glomerular diseases.