Green tea polyphenols protect against preglomerular arteriopathy via the jagged1/notch1 pathway

Preglomerular arteriopathy (PA) induced by hyperuricemia contributes to the progression of chronic kidney disease (CKD). Green tea polyphenols (GTPs) are antioxidant ingredients thought to assist in preventing hyperuricemia. However, the underlying mechanism by which GTPs affect renal function remains unclear. Both normal and remnant kidney (RK) rats were administrated oxonic acid (OX) to induce hyperuricemia. The hyperuricemia RK rats were concomitantly treated with GTPs. Hematoxlyin-eosin (H&E) and periodic acid-Schiff (PAS) staining methods were used to examine renal function and arterial morphology. The expression of proteins in the Jagged1/Notch1 pathway was assessed via immunohistochemistry, in situ hybridization, the quantitative polymerase chain reaction (qPCR), and western blotting techniques. Our results showed that an RK rat model with preglomerular vascular disease had been successfully established. Treatment of the RK rats with GTPs effectively alleviated the damage due to preglomerular arteriopathy, significantly alleviated pathological symptoms, and reduced the levels of proteinuria, serum UA, BUN, and creatinine. Our results also suggested involvement of the Jagged1/Notch1 pathway in the preglomerular vascular lesions. The levels of Jagged1, Notch1-ICD, Hes5, and p-STAT3 were significantly decreased in RK + OA-treated rats when compared with those in RK rats. Treatment with GTPs upregulated the levels of Jagged1, Notch1, Hes5, p-STAT3, and MnSOD2, and downregulated xanthine oxidase (XO) expression in rats with preglomerular arteriopathy. However, the beneficial effects of GTPs were lost when the Jagged1/Notch1-STAT3 pathway was inactivated by siRNA. In conclusion, GTPs exert a therapeutic effect on perglomerular arteriopathy. Our results also revealed a novel mechanism that mediates preglomerular arteriopathy, and suggest GTPs as effective novel renal protective agents.