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eISSN: 1643-3750

Genistein and Myd88 Activate Autophagy in High Glucose-Induced Renal Podocytes In Vitro

Yuanyuan Wang, Ying Li, Tao Zhang, Yanqing Chi, Maodong Liu, Ying Liu

(Department of Nephrology, Hebei Medical University Third Affiliated Hospital, Shijiazhuang, Hebei, China (mainland))

Med Sci Monit 2018; 24:4823-4831

DOI: 10.12659/MSM.910868

Published: 2018-07-12


BACKGROUND: Renal podocyte damage plays a crucial role in the development of diabetic nephropathy. Genistein is derived from a leguminous plant, and MyD88 and TRIF are adaptor molecules in the Toll-like receptor (TLR) signaling pathway, which may play a role in autophagy. In this study, we utilized an in vitro high glucose (HG)-treated podocyte model to investigate the effects and underlying mechanisms of Genistein and MyD88 or TRIF siRNA induced autophagy and renal protection.
MATERIAL AND METHODS: An immortalized mouse podocyte cell line was treated with HG, Genistein, chloroquine, and/or transfected with specific Myd88 and TRIF siRNAs. The formation of autophagosomes and related autophagic vacuoles were monitored by transmission electron microscopy. The expression of autophagy-related factors and podocyte structure and functional markers, including LC3, p62, p-mTOR, synaptopodin, and nephrin, were measured by Western blot, and LC3 and p-mTOR expression were also assessed by immunofluorescence.
RESULTS: We showed that HG transiently (after 6-h exposure) induced expression of the autophagy activation marker LC3-II in podocytes. Genistein treatment induced autophagy in both normal and HG-treated podocytes through inactivating mTOR signaling. Moreover, Genistein protected podocytes against chloroquine in HG-cultured conditions in vitro by maintaining the level of autophagy-related proteins. In addition, MyD88 siRNA downregulated expression of autophagy-related proteins, whereas Genistein treatment reversed these effects.
CONCLUSIONS: This study demonstrated that Genistein-induced autophagy could be a potential treatment strategy for glomerular diseases.

Keywords: Autophagy, Diabetic Nephropathies, Genistein, Podocytes



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