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- W4200433164 abstract "Abstract Background LncRNA AK044604 (Risa), Sirt1 and GSK3β are autophagy related genes that can play important roles in diabetic nephropathy (DN). In this study, we sought to explore the effect of Risa on Sirt1/GSK3β-induced podocyte injury. Methods Transgenic db/db mice were fed and injected with Risa inhibition of adeno-associated virus by tail vein injection, as well as intraperitoneally injected with LiCl. Blood, urine, kidney tissue samples, and clinical data were collected at different time points. Immortalized mouse podocyte cells (MPCs) were cultured and treated with Risa inhibition of lentivirus, EX-527, and LiCl. MPCs were collected under different stimulations. The effects of Risa on podocyte autophagy were examined by qRT-PCR, Western blot analysis, transmission electron microscope, PAS staining, and immunofluorescence staining. Results Risa and activated GSK3β were overexpressed, but Sirt1 decreased in Renal tissues of DN mice and high-glucose-treated MPCs and correlated with poor prognosis. Risa overexpression attenuated Sirt1-mediated downstream autophagy levels and aggravated the injury of podocytes by inhibiting the expression of Sirt1. In contrast, Risa inhibition enhanced Sirt1-induced autophagy and attenuated podocyte injury, but this effect could be abrogated by EX-527, suggesting that Risa overexpression aggravated podocyte injury by decreasing autophagy. Conclusions Risa inhibits autophagy by regulating the Sirt1/GSK3β axis and thereby aggravates podocyte injury in DN. Risa may serve as a therapeutic target for the treatment of DN." @default.
- W4200433164 created "2021-12-31" @default.
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- W4200433164 date "2021-11-16" @default.
- W4200433164 modified "2023-09-29" @default.
- W4200433164 title "Down-regulation of Risa Improves Podocyte Injury by Enhancing Autophagy in Diabetic Nephropathy" @default.
- W4200433164 doi "https://doi.org/10.21203/rs.3.rs-989734/v1" @default.
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