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

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...

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Autores principales: Wang, Yuanyuan, Li, Ying, Zhang, Tao, Chi, Yanqing, Liu, Maodong, Liu, Ying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: International Scientific Literature, Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6069420/
https://www.ncbi.nlm.nih.gov/pubmed/29999001
http://dx.doi.org/10.12659/MSM.910868
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author Wang, Yuanyuan
Li, Ying
Zhang, Tao
Chi, Yanqing
Liu, Maodong
Liu, Ying
author_facet Wang, Yuanyuan
Li, Ying
Zhang, Tao
Chi, Yanqing
Liu, Maodong
Liu, Ying
author_sort Wang, Yuanyuan
collection PubMed
description 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/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.
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spelling pubmed-60694202018-08-01 Genistein and Myd88 Activate Autophagy in High Glucose-Induced Renal Podocytes In Vitro Wang, Yuanyuan Li, Ying Zhang, Tao Chi, Yanqing Liu, Maodong Liu, Ying Med Sci Monit Lab/In Vitro Research 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/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. International Scientific Literature, Inc. 2018-07-12 /pmc/articles/PMC6069420/ /pubmed/29999001 http://dx.doi.org/10.12659/MSM.910868 Text en © Med Sci Monit, 2018 This work is licensed under Creative Common Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) )
spellingShingle Lab/In Vitro Research
Wang, Yuanyuan
Li, Ying
Zhang, Tao
Chi, Yanqing
Liu, Maodong
Liu, Ying
Genistein and Myd88 Activate Autophagy in High Glucose-Induced Renal Podocytes In Vitro
title Genistein and Myd88 Activate Autophagy in High Glucose-Induced Renal Podocytes In Vitro
title_full Genistein and Myd88 Activate Autophagy in High Glucose-Induced Renal Podocytes In Vitro
title_fullStr Genistein and Myd88 Activate Autophagy in High Glucose-Induced Renal Podocytes In Vitro
title_full_unstemmed Genistein and Myd88 Activate Autophagy in High Glucose-Induced Renal Podocytes In Vitro
title_short Genistein and Myd88 Activate Autophagy in High Glucose-Induced Renal Podocytes In Vitro
title_sort genistein and myd88 activate autophagy in high glucose-induced renal podocytes in vitro
topic Lab/In Vitro Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6069420/
https://www.ncbi.nlm.nih.gov/pubmed/29999001
http://dx.doi.org/10.12659/MSM.910868
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