Aim of the study
To evaluate the therapeutic effect and further explore the therapeutic mechanism of QYYYG against HRD. Materials and
Conclusions
The present study suggested that QYYYG may exert its HRD protective effects in part by regulating the abnormal autophagy of podocytes through the TRPC6-CaMKKβ-AMPK-mTOR pathway.
Methods
The efficacy of QYYYG in treating HRD was assessed in spontaneous hypertension rats (SHR). Renal autophagy and the TRPC6-CaMKKβ-AMPK pathway in rats were evaluated. The regulatory role of QYYYG in angiotensin II (Ang II) induced abnormal autophagy in rat podocytes was determined by detecting autophagy-related proteins, intracellular Ca2+ content, and the TRPC6-CaMKKβ-AMPK-mTOR pathway expressions. Finally, we established a stable rat podocyte cell line overexpressing TRPC6 and used the cells to verify the regulatory effects of QYYYG.
Results
QYYYG alleviated HRD and reversed the abnormal expression of autophagy-related genes in the SHR. In vitro, QYYYG protected against Ang II-induced podocyte damage. Furthermore, treatment of podocytes with QYYYG reversed Ang II-induced autophagy and inhibited Ang II-stimulated TRPC6 activation, Ca2+ influx and activation CaMKKβ-AMPK pathway. Overexpression of TRPC6 resulted in pronounced activation of CaMKKβ, AMPK, and autophagy induction in rat podocytes, which were significantly attenuated by QYYYG. Conclusions: The present study suggested that QYYYG may exert its HRD protective effects in part by regulating the abnormal autophagy of podocytes through the TRPC6-CaMKKβ-AMPK-mTOR pathway.