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 language | English |
|---|---|
| Pages (from-to) | 61-72 |
| Number of pages | 12 |
| Journal | Nephrology Dialysis Transplantation |
| Volume | 32 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2017 Jan 1 |
Fingerprint
All Science Journal Classification (ASJC) codes
- Nephrology
- Transplantation
Cite this
}
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 journal › Article
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.
UR - http://www.scopus.com/inward/record.url?scp=85016193519&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85016193519&partnerID=8YFLogxK
U2 - 10.1093/ndt/gfw089
DO - 10.1093/ndt/gfw089
M3 - Article
C2 - 27358275
AN - SCOPUS:85016193519
VL - 32
SP - 61
EP - 72
JO - Nephrology Dialysis Transplantation
JF - Nephrology Dialysis Transplantation
SN - 0931-0509
IS - 1
ER -