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Enhanced glycogen synthase kinase-3β activity mediates podocyte apoptosis under diabetic conditions

 Jisun Paeng  ;  Jae Hyun Chang  ;  Sun Ha Lee  ;  Bo Young Nam  ;  Hye-Young Kang  ;  Seonghun Kim  ;  Hyung Jung Oh  ;  Jung Tak Park  ;  Seung Hyeok Han  ;  Tae-Hyun Yoo  ;  Shin-Wook Kang 
 Apoptosis, Vol.19(12) : 1678-1690, 2014 
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Glycogen synthase kinase-3β (GSK-3β) is involved in the pathogenesis of various kidney diseases. This study was undertaken to examine the changes in GSK-3β activity in podocytes under diabetic conditions and to elucidate the functional role of GSK-3β in podocyte apoptosis. In vivo, 32 rats were injected with either diluent (n = 16, C) or with streptozotocin intraperitoneally (n = 16, DM), and 8 rats from each group were treated with 6-bromoindirubin-3'-oxime (BIO) for 3 months. In vitro, immortalized mouse podocytes were exposed to 5.6 mM glucose or 30 mM glucose (HG) with or without 10 μM BIO. Western blot analysis and TUNEL or Hoechst 33342 staining were performed to identify apoptosis. Urinary albumin excretion was significantly higher in DM rats, and this increase was significantly abrogated in DM rats by BIO treatment. The protein expression of Tyr216-phospho-GSK-3β was significantly increased in DM glomeruli and in cultured podocytes exposed to HG. Western blot analysis revealed that the protein expression of Bax and active fragments of caspase-3 were significantly increased, whereas phospho-Akt, β-catenin, and Bcl-2 protein expression were significantly decreased in DM glomeruli and HG-stimulated podocytes. Apoptosis, determined by TUNEL assay and Hoechst 33342 staining, was also significantly increased in podocytes under diabetic conditions. The changes in the expression of apoptosis-related molecules and the increase in the number of apoptotic cells in DM glomeruli as well as in HG-stimulated podocytes were significantly ameliorated by BIO. These findings suggest that enhanced GSK-3β activity within podocytes under diabetic conditions is associated with podocyte loss in diabetic nephropathy.
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1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실)
Yonsei Authors
강신욱(Kang, Shin Wook) ORCID logo https://orcid.org/0000-0002-5677-4756
강혜영(Kang, Hye Young)
김성훈(Kim, Seonghun)
남보영(Nam, Bo Young)
박정탁(Park, Jung Tak) ORCID logo https://orcid.org/0000-0002-2325-8982
오형중(Oh, Hyung Jung)
유태현(Yoo, Tae Hyun) ORCID logo https://orcid.org/0000-0002-9183-4507
이순하(Lee, Sun Ha)
장제현(Chang, Jae Hyun)
팽지선(Paeng, Ji Sun)
한승혁(Han, Seung Hyeok) ORCID logo https://orcid.org/0000-0001-7923-5635
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