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

doi:10.1093/ndt/gfh642

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

Department of Internal Medicine

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Abstract

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^-7M 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±0.20 × 10^-2 attm/ng RNA) than in C rats (2.61±0.33 × 10^-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.

Original language	English
Pages (from-to)	524-531
Number of pages	8
Journal	Nephrology Dialysis Transplantation
Volume	20
Issue number	3
DOIs	https://doi.org/10.1093/ndt/gfh642
Publication status	Published - 2005 Mar

Bibliographical note

Funding Information:
Acknowledgements. The authors are thankful to Dr Peter Mundel (Albert Einstein College of Medicine, Bronx, NY, USA) for kindly providing us with the immortalized mouse podocyte cell line. This work was supported by a Korea Research Foundation grant (KRF-2002-042-E00045) and grants from the Juvenile Diabetes Research Foundation (to S.G.A. and R.N.) and the National Institutes of Health (RO1-DK58191) (to R.N.).

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Nephrology
Transplantation

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10.1093/ndt/gfh642

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Xu, Zhong Gao ; Ryu, Dong Ryeol ; Yoo, Tae Hyun ; Jung, Dong Sub ; Kim, Jin Ju ; Kim, Hyung Jong ; Choi, Hoon Young ; Kim, Joo Seong ; Adler, Sharon G. ; Natarajan, Rama ; Han, Dae Suk ; Kang, Shin Wook. / P-cadherin is decreased in diabetic glomeruli and in glucose-stimulated podocytes in vivo and in vitro studies. In: Nephrology Dialysis Transplantation. 2005 ; Vol. 20, No. 3. pp. 524-531.

@article{3c2514e0940745d38ca8acb8329823d7,

title = "P-cadherin is decreased in diabetic glomeruli and in glucose-stimulated podocytes in vivo and in vitro studies",

abstract = "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 (10-7M 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±0.20 × 10-2 attm/ng RNA) than in C rats (2.61±0.33 × 10-2 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.",

author = "Xu, {Zhong Gao} and Ryu, {Dong Ryeol} and Yoo, {Tae Hyun} and Jung, {Dong Sub} and Kim, {Jin Ju} and Kim, {Hyung Jong} and Choi, {Hoon Young} and Kim, {Joo Seong} and Adler, {Sharon G.} and Rama Natarajan and Han, {Dae Suk} and Kang, {Shin Wook}",

note = "Funding Information: Acknowledgements. The authors are thankful to Dr Peter Mundel (Albert Einstein College of Medicine, Bronx, NY, USA) for kindly providing us with the immortalized mouse podocyte cell line. This work was supported by a Korea Research Foundation grant (KRF-2002-042-E00045) and grants from the Juvenile Diabetes Research Foundation (to S.G.A. and R.N.) and the National Institutes of Health (RO1-DK58191) (to R.N.).",

year = "2005",

month = mar,

doi = "10.1093/ndt/gfh642",

language = "English",

volume = "20",

pages = "524--531",

journal = "Nephrology Dialysis Transplantation",

issn = "0931-0509",

publisher = "Oxford University Press",

number = "3",

}

P-cadherin is decreased in diabetic glomeruli and in glucose-stimulated podocytes in vivo and in vitro studies. / Xu, Zhong Gao; Ryu, Dong Ryeol; Yoo, Tae Hyun; Jung, Dong Sub; Kim, Jin Ju; Kim, Hyung Jong; Choi, Hoon Young; Kim, Joo Seong; Adler, Sharon G.; Natarajan, Rama; Han, Dae Suk; Kang, Shin Wook.

In: Nephrology Dialysis Transplantation, Vol. 20, No. 3, 03.2005, p. 524-531.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - P-cadherin is decreased in diabetic glomeruli and in glucose-stimulated podocytes in vivo and in vitro studies

AU - Xu, Zhong Gao

AU - Ryu, Dong Ryeol

AU - Yoo, Tae Hyun

AU - Jung, Dong Sub

AU - Kim, Jin Ju

AU - Kim, Hyung Jong

AU - Choi, Hoon Young

AU - Kim, Joo Seong

AU - Adler, Sharon G.

AU - Natarajan, Rama

AU - Han, Dae Suk

AU - Kang, Shin Wook

N1 - Funding Information: Acknowledgements. The authors are thankful to Dr Peter Mundel (Albert Einstein College of Medicine, Bronx, NY, USA) for kindly providing us with the immortalized mouse podocyte cell line. This work was supported by a Korea Research Foundation grant (KRF-2002-042-E00045) and grants from the Juvenile Diabetes Research Foundation (to S.G.A. and R.N.) and the National Institutes of Health (RO1-DK58191) (to R.N.).

PY - 2005/3

Y1 - 2005/3

N2 - 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 (10-7M 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±0.20 × 10-2 attm/ng RNA) than in C rats (2.61±0.33 × 10-2 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.

AB - 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 (10-7M 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±0.20 × 10-2 attm/ng RNA) than in C rats (2.61±0.33 × 10-2 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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UR - http://www.scopus.com/inward/citedby.url?scp=20144381750&partnerID=8YFLogxK

U2 - 10.1093/ndt/gfh642

DO - 10.1093/ndt/gfh642

M3 - Article

C2 - 15647309

AN - SCOPUS:20144381750

VL - 20

SP - 524

EP - 531

JO - Nephrology Dialysis Transplantation

JF - Nephrology Dialysis Transplantation

SN - 0931-0509

IS - 3

ER -

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

Abstract

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