The locally activated renin-angiotensin system is involved in albumin permeability in glomerular endothelial cells under high glucose conditions

Jisun Paeng, Jimin Park, Jae Eun Um, Bo Young Nam, Hye Young Kang, Seonghun Kim, Hyung Jung Oh, Jung Tak Park, SeungHyeok Han, Dong Ryeol Ryu, TaeHyun Yoo, Shin-Wook Kang

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background. Although the diabetic milieu per se, hemodynamic changes, oxidative stress and local growth factors such as angiotensin II (AII) are considered to bemediators in the pathogenesis of diabetic nephropathy, the underlying pathways mediating the changes in glomerular endothelial cells (GECs) are not well understood. Therefore, we investigated changes in the reninangiotensin system (RAS) components in high glucose (HG)- stimulated GECs and the role of the local RAS in morphological and functional changes in GECs under diabetic conditions. Methods. We stimulated GECs with 5.6 mM glucose or 30 mM glucose with or without an angiotensin II type I receptor blocker (ARB) in vitro and also performed experiments with Sprague- Dawley rats injected with diluent (n = 16) or streptozotocin [n = 16, diabetes (DM)]. Eight rats from each group were treated with ARB for 3months in vivo. Real-time polymerase chain reaction, western blot analysis, enzyme-linked immunosorbent assay and immunofluorescent staining using cultured GECs were performed. The permeability of GECs to macromolecules was assessed by measuring the passage of fluorescein isothiocyanatelabeled bovine serum albumin.Morphological changes were also evaluated by scanning and transmission electronmicroscopy. Results. There were significant increases in angiotensinogen expression in HG-stimulated GECs along with significant increases in AI and AII levels. Moreover, the expression of heparan sulfate glycosaminoglycans (HS-GAG) assessed by immunofluorescent staining was significantly lower and the permeability to albumin was significantly higher in GECs exposed to HG medium, and ARB treatment significantly abrogated these changes. Upon electron microscopy examination, the mean size of the GEC fenestrae was significantly greater in HG-stimulated GECs and DM rats, and these increases were significantly ameliorated by ARB. Conclusions. The local RAS within GECs was activated under HG conditions, and this activation may be associated with both an alteration in GEC fenestration and a decrease in HS-GAG, resulting in the development of albuminuria in diabetic nephropathy.

Original languageEnglish
Pages (from-to)61-72
Number of pages12
JournalNephrology Dialysis Transplantation
Volume32
Issue number1
DOIs
Publication statusPublished - 2017 Jan 1

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Renin-Angiotensin System
Albumins
Permeability
Endothelial Cells
Glucose
Heparitin Sulfate
Diabetic Nephropathies
Glycosaminoglycans
Angiotensin II
Staining and Labeling
Angiotensin I
Angiotensinogen
Albuminuria
Angiotensin Receptor Antagonists
Streptozocin
Bovine Serum Albumin
Fluorescein
Sprague Dawley Rats
Real-Time Polymerase Chain Reaction
Intercellular Signaling Peptides and Proteins

All Science Journal Classification (ASJC) codes

  • Nephrology
  • Transplantation

Cite this

Paeng, Jisun ; Park, Jimin ; Um, Jae Eun ; Nam, Bo Young ; Kang, Hye Young ; Kim, Seonghun ; Oh, Hyung Jung ; Park, Jung Tak ; Han, SeungHyeok ; Ryu, Dong Ryeol ; Yoo, TaeHyun ; Kang, Shin-Wook. / The locally activated renin-angiotensin system is involved in albumin permeability in glomerular endothelial cells under high glucose conditions. In: Nephrology Dialysis Transplantation. 2017 ; Vol. 32, No. 1. pp. 61-72.
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abstract = "Background. Although the diabetic milieu per se, hemodynamic changes, oxidative stress and local growth factors such as angiotensin II (AII) are considered to bemediators in the pathogenesis of diabetic nephropathy, the underlying pathways mediating the changes in glomerular endothelial cells (GECs) are not well understood. Therefore, we investigated changes in the reninangiotensin system (RAS) components in high glucose (HG)- stimulated GECs and the role of the local RAS in morphological and functional changes in GECs under diabetic conditions. Methods. We stimulated GECs with 5.6 mM glucose or 30 mM glucose with or without an angiotensin II type I receptor blocker (ARB) in vitro and also performed experiments with Sprague- Dawley rats injected with diluent (n = 16) or streptozotocin [n = 16, diabetes (DM)]. Eight rats from each group were treated with ARB for 3months in vivo. Real-time polymerase chain reaction, western blot analysis, enzyme-linked immunosorbent assay and immunofluorescent staining using cultured GECs were performed. The permeability of GECs to macromolecules was assessed by measuring the passage of fluorescein isothiocyanatelabeled bovine serum albumin.Morphological changes were also evaluated by scanning and transmission electronmicroscopy. Results. There were significant increases in angiotensinogen expression in HG-stimulated GECs along with significant increases in AI and AII levels. Moreover, the expression of heparan sulfate glycosaminoglycans (HS-GAG) assessed by immunofluorescent staining was significantly lower and the permeability to albumin was significantly higher in GECs exposed to HG medium, and ARB treatment significantly abrogated these changes. Upon electron microscopy examination, the mean size of the GEC fenestrae was significantly greater in HG-stimulated GECs and DM rats, and these increases were significantly ameliorated by ARB. Conclusions. The local RAS within GECs was activated under HG conditions, and this activation may be associated with both an alteration in GEC fenestration and a decrease in HS-GAG, resulting in the development of albuminuria in diabetic nephropathy.",
author = "Jisun Paeng and Jimin Park and Um, {Jae Eun} and Nam, {Bo Young} and Kang, {Hye Young} and Seonghun Kim and Oh, {Hyung Jung} and Park, {Jung Tak} and SeungHyeok Han and Ryu, {Dong Ryeol} and TaeHyun Yoo and Shin-Wook Kang",
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The locally activated renin-angiotensin system is involved in albumin permeability in glomerular endothelial cells under high glucose conditions. / Paeng, Jisun; Park, Jimin; Um, Jae Eun; Nam, Bo Young; Kang, Hye Young; Kim, Seonghun; Oh, Hyung Jung; Park, Jung Tak; Han, SeungHyeok; Ryu, Dong Ryeol; Yoo, TaeHyun; Kang, Shin-Wook.

In: Nephrology Dialysis Transplantation, Vol. 32, No. 1, 01.01.2017, p. 61-72.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The locally activated renin-angiotensin system is involved in albumin permeability in glomerular endothelial cells under high glucose conditions

AU - Paeng, Jisun

AU - Park, Jimin

AU - Um, Jae Eun

AU - Nam, Bo Young

AU - Kang, Hye Young

AU - Kim, Seonghun

AU - Oh, Hyung Jung

AU - Park, Jung Tak

AU - Han, SeungHyeok

AU - Ryu, Dong Ryeol

AU - Yoo, TaeHyun

AU - Kang, Shin-Wook

PY - 2017/1/1

Y1 - 2017/1/1

N2 - Background. Although the diabetic milieu per se, hemodynamic changes, oxidative stress and local growth factors such as angiotensin II (AII) are considered to bemediators in the pathogenesis of diabetic nephropathy, the underlying pathways mediating the changes in glomerular endothelial cells (GECs) are not well understood. Therefore, we investigated changes in the reninangiotensin system (RAS) components in high glucose (HG)- stimulated GECs and the role of the local RAS in morphological and functional changes in GECs under diabetic conditions. Methods. We stimulated GECs with 5.6 mM glucose or 30 mM glucose with or without an angiotensin II type I receptor blocker (ARB) in vitro and also performed experiments with Sprague- Dawley rats injected with diluent (n = 16) or streptozotocin [n = 16, diabetes (DM)]. Eight rats from each group were treated with ARB for 3months in vivo. Real-time polymerase chain reaction, western blot analysis, enzyme-linked immunosorbent assay and immunofluorescent staining using cultured GECs were performed. The permeability of GECs to macromolecules was assessed by measuring the passage of fluorescein isothiocyanatelabeled bovine serum albumin.Morphological changes were also evaluated by scanning and transmission electronmicroscopy. Results. There were significant increases in angiotensinogen expression in HG-stimulated GECs along with significant increases in AI and AII levels. Moreover, the expression of heparan sulfate glycosaminoglycans (HS-GAG) assessed by immunofluorescent staining was significantly lower and the permeability to albumin was significantly higher in GECs exposed to HG medium, and ARB treatment significantly abrogated these changes. Upon electron microscopy examination, the mean size of the GEC fenestrae was significantly greater in HG-stimulated GECs and DM rats, and these increases were significantly ameliorated by ARB. Conclusions. The local RAS within GECs was activated under HG conditions, and this activation may be associated with both an alteration in GEC fenestration and a decrease in HS-GAG, resulting in the development of albuminuria in diabetic nephropathy.

AB - Background. Although the diabetic milieu per se, hemodynamic changes, oxidative stress and local growth factors such as angiotensin II (AII) are considered to bemediators in the pathogenesis of diabetic nephropathy, the underlying pathways mediating the changes in glomerular endothelial cells (GECs) are not well understood. Therefore, we investigated changes in the reninangiotensin system (RAS) components in high glucose (HG)- stimulated GECs and the role of the local RAS in morphological and functional changes in GECs under diabetic conditions. Methods. We stimulated GECs with 5.6 mM glucose or 30 mM glucose with or without an angiotensin II type I receptor blocker (ARB) in vitro and also performed experiments with Sprague- Dawley rats injected with diluent (n = 16) or streptozotocin [n = 16, diabetes (DM)]. Eight rats from each group were treated with ARB for 3months in vivo. Real-time polymerase chain reaction, western blot analysis, enzyme-linked immunosorbent assay and immunofluorescent staining using cultured GECs were performed. The permeability of GECs to macromolecules was assessed by measuring the passage of fluorescein isothiocyanatelabeled bovine serum albumin.Morphological changes were also evaluated by scanning and transmission electronmicroscopy. Results. There were significant increases in angiotensinogen expression in HG-stimulated GECs along with significant increases in AI and AII levels. Moreover, the expression of heparan sulfate glycosaminoglycans (HS-GAG) assessed by immunofluorescent staining was significantly lower and the permeability to albumin was significantly higher in GECs exposed to HG medium, and ARB treatment significantly abrogated these changes. Upon electron microscopy examination, the mean size of the GEC fenestrae was significantly greater in HG-stimulated GECs and DM rats, and these increases were significantly ameliorated by ARB. Conclusions. The local RAS within GECs was activated under HG conditions, and this activation may be associated with both an alteration in GEC fenestration and a decrease in HS-GAG, resulting in the development of albuminuria in diabetic nephropathy.

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