Peroxisome proliferator-activated receptor-δ activation ameliorates albuminuria by preventing nephrin loss and restoring podocyte integrity in Type 2 diabetes

Eun Young Lee, Geun Tae Kim, Miri Hyun, Suji Kim, Sujin Seok, Ran Choi, Mi Young Lee, Choon Hee Chung

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13 Citations (Scopus)

Abstract

BackgroundPeroxisome proliferator-activated receptor (PPAR)-δ is a ligand-activated transcription factor in regulating gene expression and is believed to play an important role in various kidney diseases including diabetic nephropathy. This study investigated the efficacy of GW610742, a highly specific agonist for PPAR-δ, for the treatment of diabetic nephropathy.MethodsType 2 diabetic Otsuka Long-Evans Tokushima Fatty rats were randomized into an untreated diabetic group (n = 9) and a GW610742-treated diabetic group (n = 9). The GW610742 was administered (10 mg/kg/day) orally for 11 weeks. Long-Evans Tokushima Otsuka rats (n = 9) were used as a non-diabetic control.ResultsAlbuminuria was markedly increased and renal PPAR-δ expression was decreased in diabetes. Diabetic albuminuria and renal injury markers, such as glomerular basement membrane thickening, decreased number of slit pores between podocyte foot processes, decreased nephrin expression, increased desmin expression and increased CCL2 expression, were significantly reversed through the treatment with GW610742. PPAR-δ agonist GW610742 markedly increased nephrin expression in cultured podocytes. Nephrin mRNA expression was markedly decreased in response to high glucose in cultured podocytes and effectively prevented by GW610742.ConclusionsPPAR-δ activation by GW610742 ameliorates albuminuria by preventing diabetes-induced nephrin loss and restoring podocyte integrity, implying that GW610742 may be a potential therapeutic agent for diabetic nephropathy.

Original languageEnglish
Pages (from-to)4069-4079
Number of pages11
JournalNephrology Dialysis Transplantation
Volume27
Issue number11
DOIs
Publication statusPublished - 2012 Nov 1

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Podocytes
Peroxisome Proliferator-Activated Receptors
Albuminuria
Type 2 Diabetes Mellitus
Diabetic Nephropathies
Inbred OLETF Rats
Kidney
Glomerular Basement Membrane
Desmin
GW 610742
nephrin
Kidney Diseases
Transcription Factors
Ligands
Gene Expression
Glucose
Messenger RNA
Wounds and Injuries

All Science Journal Classification (ASJC) codes

  • Nephrology
  • Transplantation

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Lee, Eun Young ; Kim, Geun Tae ; Hyun, Miri ; Kim, Suji ; Seok, Sujin ; Choi, Ran ; Lee, Mi Young ; Chung, Choon Hee. / Peroxisome proliferator-activated receptor-δ activation ameliorates albuminuria by preventing nephrin loss and restoring podocyte integrity in Type 2 diabetes. In: Nephrology Dialysis Transplantation. 2012 ; Vol. 27, No. 11. pp. 4069-4079.
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abstract = "BackgroundPeroxisome proliferator-activated receptor (PPAR)-δ is a ligand-activated transcription factor in regulating gene expression and is believed to play an important role in various kidney diseases including diabetic nephropathy. This study investigated the efficacy of GW610742, a highly specific agonist for PPAR-δ, for the treatment of diabetic nephropathy.MethodsType 2 diabetic Otsuka Long-Evans Tokushima Fatty rats were randomized into an untreated diabetic group (n = 9) and a GW610742-treated diabetic group (n = 9). The GW610742 was administered (10 mg/kg/day) orally for 11 weeks. Long-Evans Tokushima Otsuka rats (n = 9) were used as a non-diabetic control.ResultsAlbuminuria was markedly increased and renal PPAR-δ expression was decreased in diabetes. Diabetic albuminuria and renal injury markers, such as glomerular basement membrane thickening, decreased number of slit pores between podocyte foot processes, decreased nephrin expression, increased desmin expression and increased CCL2 expression, were significantly reversed through the treatment with GW610742. PPAR-δ agonist GW610742 markedly increased nephrin expression in cultured podocytes. Nephrin mRNA expression was markedly decreased in response to high glucose in cultured podocytes and effectively prevented by GW610742.ConclusionsPPAR-δ activation by GW610742 ameliorates albuminuria by preventing diabetes-induced nephrin loss and restoring podocyte integrity, implying that GW610742 may be a potential therapeutic agent for diabetic nephropathy.",
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Peroxisome proliferator-activated receptor-δ activation ameliorates albuminuria by preventing nephrin loss and restoring podocyte integrity in Type 2 diabetes. / Lee, Eun Young; Kim, Geun Tae; Hyun, Miri; Kim, Suji; Seok, Sujin; Choi, Ran; Lee, Mi Young; Chung, Choon Hee.

In: Nephrology Dialysis Transplantation, Vol. 27, No. 11, 01.11.2012, p. 4069-4079.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Peroxisome proliferator-activated receptor-δ activation ameliorates albuminuria by preventing nephrin loss and restoring podocyte integrity in Type 2 diabetes

AU - Lee, Eun Young

AU - Kim, Geun Tae

AU - Hyun, Miri

AU - Kim, Suji

AU - Seok, Sujin

AU - Choi, Ran

AU - Lee, Mi Young

AU - Chung, Choon Hee

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N2 - BackgroundPeroxisome proliferator-activated receptor (PPAR)-δ is a ligand-activated transcription factor in regulating gene expression and is believed to play an important role in various kidney diseases including diabetic nephropathy. This study investigated the efficacy of GW610742, a highly specific agonist for PPAR-δ, for the treatment of diabetic nephropathy.MethodsType 2 diabetic Otsuka Long-Evans Tokushima Fatty rats were randomized into an untreated diabetic group (n = 9) and a GW610742-treated diabetic group (n = 9). The GW610742 was administered (10 mg/kg/day) orally for 11 weeks. Long-Evans Tokushima Otsuka rats (n = 9) were used as a non-diabetic control.ResultsAlbuminuria was markedly increased and renal PPAR-δ expression was decreased in diabetes. Diabetic albuminuria and renal injury markers, such as glomerular basement membrane thickening, decreased number of slit pores between podocyte foot processes, decreased nephrin expression, increased desmin expression and increased CCL2 expression, were significantly reversed through the treatment with GW610742. PPAR-δ agonist GW610742 markedly increased nephrin expression in cultured podocytes. Nephrin mRNA expression was markedly decreased in response to high glucose in cultured podocytes and effectively prevented by GW610742.ConclusionsPPAR-δ activation by GW610742 ameliorates albuminuria by preventing diabetes-induced nephrin loss and restoring podocyte integrity, implying that GW610742 may be a potential therapeutic agent for diabetic nephropathy.

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