Effects of apigenin on mesangial GATA3 expression and PDGFR-β/NF-κB signaling pathway in experimental diabetic...

Diabetic nephropathy (DN) is the most common microvascular complication of diabetes and leading cause of end-stage renal disease (ESRD) requiring dialysis. Mesangial cell proliferation induced by hyperglycemia is a hallmark of DN. Apigenin, a compound abundantly present in fruits and vegetables, exhibit anti-inflammatory and antioxidant properties and have shown potential in alleviating DN. In this study, for the first time, the effect of Apigenin on mesangial cell proliferation in an experimental DN model induced by Streptozotosin (STZ) injection was evaluated through Gata3, Pdgfr-β and Nf-κb expressions. 42 male Wistar rats were divided randomly into seven groups as intact control, sham, Apigenin, Pyrrolidine Dithiocarbamate (PDTC), DN + Apigenin and DN + PDTC. Kidney tissue and blood serum samples from all groups were evaluated using light and electron microscopy, immunohistochemical, molecular biological, and biochemical methods. It was found that Gata3, Pdgfr-β and Nf-κb expressions were upregulated in DN group, while their expressions were significantly decreased in DN + Apigenin and DN + PDTC groups. Histopathologic examinations revealed diffuse and nodular glomerulosclerosis due to mesangial proliferation, fibrosis and severe degenerative changes of tubular cells and renal corpuscles in DN group, whereas a reduction in renal damage related to DN was observed in DN + Apigenin group. Interestingly, in our study, downregulation of Pdgfr-β expression with PDTC compared to the DN + Apigenin group, suggested an effective feedback mechanism between Pdgfr-β and Nf-κb. In DN, the expression of Gata3 and Nf-κb both upregulated through the PDGFR-β/NF-κB signaling pathway is attenuated by Apigenin treatment. It is concluded that Apigenin, as an anti-glomerulosclerotic therapeutic agent.