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

Background: The protein kinase C (PKC) family consists of thirteen members categorized as conventional or novel depending on whether diaclyglycerol, 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 B was reported to have positive role in B lymphocyte activity through activation of NF-kB leading to various immune disorders. We examined renal gene expression of two PKC isoforms α β 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. Methods: PKC α β gene expression was studied by quantitative real-time Reverse Transcription-PCR in 20 patients with type II 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/1.73m2 ), 20 patients with proliferative lupus nephritis (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 mL/ min/m2 ) and 20 patients with mesangioproliferative glomerulonephritis (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 m2). Normal tissues from the normal pole of 4 kidneys removed because of renal tumor served as controls. Results: PKC a gene expression was significantly increased in diabetic kidneys compared to LN and MPGN (316.95±152.94 ug/mL Vs. 185.97±32.13 ug/mL and 195.46± 46.45 ug/mL, p 0.05). PKC β gene expression was significantly increased in LN and MPGN groups compared to diabetic nephropathy group (41.01±14.03 ug/mL and 39.93+16.4lug/ mL respectively Vs. 18.20±4.91 ug/mL, p 0.05). Significant correlation was noted between the PKC a gene and proteinuria in diabetic patients. Renal expression of PKC α and β gene in control tissues was significantly lower compared to diabetic kidneys, LN and MPGN groups (32.31±0.36 and 4.6712.41 ug/ml respectively, p 0.001). Conclusion: The study demonstrated enhanced renal gene expression of both PKC isoforms α and β in diabetic kidney tissues, lupus nephritis and mesangioproliferative glomerulonephritis but in different pattern. PKC α gene expression was significantly increased in diabetic patients with chronic kidney disease compared to lupus nephritis and mesangioproliferative glomerulonephritis groups. The in- creased expression of PKC β gene in lupus nephritis and mesangioproliferative glomerulonephritis highlights its role in regulation of immune system. This may represent potential therapeutic targets for prevention of progressive kidney injury in diabetic and proliferative glomerular diseases.