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P-Cadherin is decreased in diabetic glomeruli and in glucose-stimulated podocytes in vivo and in vitro studies

 Zhong-Gao Xu  ;  Dong-Ryeol Ryu  ;  Tae-Hyun Yoo  ;  Dong-Sub Jung  ;  Jin-Ju Kim  ;  Hyung-Jong Kim  ;  Hoon-Young Choi  ;  Joo-Seong Kim  ;  Sharon G. Adler  ;  Rama Natarajan  ;  Dae-Suk Han  ;  Shin-Wook Kang 
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P-cadherin ; diabetic nephropathy ; high glucose ; podocyte ; proteinuria
P-cadherin ; diabetic nephropathy ; high glucose ; podocyte ; proteinuria
BACKGROUND: Proteinuria is a cardinal feature of glomerular disease, including diabetic nephropathy, and the glomerular filtration barrier acts as a filter, restricting protein excretion in urine. We tested whether the expression of P-cadherin, a molecule known to be located at the slit diaphragm, was altered by diabetes in vivo and by high glucose in vitro. METHODS: In vivo, 24 Sprague-Dawley rats were injected with diluent [control (C), n=8] or streptozotocin intraperitoneally and the latter were left untreated (DM, n=8) or treated with insulin (DM+I, n=8) for 6 weeks. In vitro, immortalized mouse podocytes were cultured in media with 5.6 mM glucose (LG), LG+19.4 mM mannitol (LG+M) or 25 mM glucose (HG) with or without protein kinase C (PKC) inhibitor (10(-7) M calphostin C or 10(-6) M GF 109203X). Reverse transcription-polymerase chain reaction, western blotting for P-cadherin mRNA and protein expression, respectively, were performed with sieved glomeruli and cell lysates, and immunofluorescence staining was undertaken with renal tissue. RESULTS: Twenty-four hour urinary albumin excretion was significantly higher in DM compared with C and DM+I rats (P<0.05). Glomerular P-cadherin mRNA expression was significantly lower in DM (1.36+/-0.20x10(-2) attm/ng RNA) than in C rats (2.61+/-0.33x10(-2) attm/ng RNA) (P<0.05). P-Cadherin protein expression, assessed by western blot and immunofluorescence staining, was also decreased in DM compared with C and DM+I glomeruli. HG significantly reduced P-cadherin mRNA and protein expression in cultured podocytes by 42% and 62%, respectively (P<0.05), and these decrements were ameliorated by PKC inhibitor. CONCLUSIONS: Diabetes in vivo and exposure of podocytes to HG in vitro reduced P-cadherin mRNA and protein expression, and PKC was involved in the regulation of HG-induced down-regulation of P-cadherin. These findings suggest that the decrease in P-cadherin expression is connected with the early changes of diabetic nephropathy and, thus, may contribute to the development of proteinuria.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Kang, Shin Wook(강신욱) ORCID logo https://orcid.org/0000-0002-5677-4756
Kim, Joo Sung(김주성)
Kim, Jin Ju(김진주)
Ryu, Dong Ryeol(류동열)
Yoo, Tae Hyun(유태현) ORCID logo https://orcid.org/0000-0002-9183-4507
Jung, Dong Sub(정동섭)
Choi, Hoon Young(최훈영) ORCID logo https://orcid.org/0000-0002-4245-0339
Han, Dae Suk(한대석)
Xu, Zhong Gao(허종호)
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