High glucose increases inducible NO production in cultured rat mesangial cells

Possible role in fibronectin production

Hyunjin Noh, Hunjoo Ha, Mi Ra Yu, Shin-Wook Kang, Kyu Hun Choi, Dae Suk Han, Ho Yung Lee

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Background/Aim: Increased nitric oxide (NO) generation and action have been suggested to be associated with glomerular hyperfiltration and increased vascular permeability early in diabetes. However, previous studies have primarily focused on the constitutive nitric oxide synthase (cNOS) pathway present in endothelial cells, and the role of the inducible NOS (iNOS) pathway in diabetic nephropathy has remained unclear. This study examined whether high glucose modulates NO synthesis by the iNOS pathway in rat mesangial cells. In addition, the effect of inhibition of the iNOS pathway on fibronectin production was determined to examine the role of the iNOS pathway in high glucose-induced extracellular expansion by mesangial cells. Methods: NO synthesis by the iNOS pathway was evaluated by nitrite and iNOS mRNA and protein productions. The effects of protein kinase C (PKC) inhibitor and aldose reductase inhibitor on the iNOS mRNA expression and aminoguanidine, a relatively specific inhibitor of the iNOS on fibronectin protein production were examined. Results: High 30 mM glucose concentration led to significant increases in nitrite production of rat mesangial cells upon stimulation with lipopolysaccharide (LPS) plus interferon-γ (IFN-γ) compared with control 5.6 mM glucose concentration. Mesangial iNOS mRNA expression and protein production also increased significantly in response to high glucose. The addition of calphostin C, a PKC inhibitor, and 6-bromo-1,3-dioxo-1H-benz[d,e]isoquinoline-2(3H)-acetic acid, an aldose reductase inhibitor, significantly suppressed the enhancement of iNOS mRNA expression in high glucose concentration. High glucose also significantly increased fibronectin protein production of mesangial cells upon stimulation with LPS plus IFN-γ compared to control glucose. Aminoguanidine reversed this high glucose-induced fibronectin production at dose inhibiting iNOS mRNA expression. Conclusions: These results indicate that high glucose enhances cytokine-induced NO production by rat mesangial cells, and that the activation of PKC and aldose reductase pathway may play a role in this enhancement. In addition, high glucose-induced NO production by the iNOS pathway may promote extracellular matrix accumulation by mesangial cells under certain condition.

Original languageEnglish
Pages (from-to)78-85
Number of pages8
JournalNephron
Volume90
Issue number1
DOIs
Publication statusPublished - 2002 Jan 16

Fingerprint

Mesangial Cells
Fibronectins
Nitric Oxide
Glucose
Aldehyde Reductase
Messenger RNA
Protein Kinase C
Protein C Inhibitor
Protein Kinase Inhibitors
Nitrites
Interferons
Lipopolysaccharides
Proteins
Diabetic Nephropathies
Capillary Permeability
Nitric Oxide Synthase Type II
Nitric Oxide Synthase
Extracellular Matrix
Endothelial Cells
Cytokines

All Science Journal Classification (ASJC) codes

  • Physiology
  • Nephrology
  • Urology
  • Physiology (medical)

Cite this

Noh, Hyunjin ; Ha, Hunjoo ; Yu, Mi Ra ; Kang, Shin-Wook ; Choi, Kyu Hun ; Han, Dae Suk ; Lee, Ho Yung. / High glucose increases inducible NO production in cultured rat mesangial cells : Possible role in fibronectin production. In: Nephron. 2002 ; Vol. 90, No. 1. pp. 78-85.
@article{a7a3900e57ac4fbda262d5183e652e8b,
title = "High glucose increases inducible NO production in cultured rat mesangial cells: Possible role in fibronectin production",
abstract = "Background/Aim: Increased nitric oxide (NO) generation and action have been suggested to be associated with glomerular hyperfiltration and increased vascular permeability early in diabetes. However, previous studies have primarily focused on the constitutive nitric oxide synthase (cNOS) pathway present in endothelial cells, and the role of the inducible NOS (iNOS) pathway in diabetic nephropathy has remained unclear. This study examined whether high glucose modulates NO synthesis by the iNOS pathway in rat mesangial cells. In addition, the effect of inhibition of the iNOS pathway on fibronectin production was determined to examine the role of the iNOS pathway in high glucose-induced extracellular expansion by mesangial cells. Methods: NO synthesis by the iNOS pathway was evaluated by nitrite and iNOS mRNA and protein productions. The effects of protein kinase C (PKC) inhibitor and aldose reductase inhibitor on the iNOS mRNA expression and aminoguanidine, a relatively specific inhibitor of the iNOS on fibronectin protein production were examined. Results: High 30 mM glucose concentration led to significant increases in nitrite production of rat mesangial cells upon stimulation with lipopolysaccharide (LPS) plus interferon-γ (IFN-γ) compared with control 5.6 mM glucose concentration. Mesangial iNOS mRNA expression and protein production also increased significantly in response to high glucose. The addition of calphostin C, a PKC inhibitor, and 6-bromo-1,3-dioxo-1H-benz[d,e]isoquinoline-2(3H)-acetic acid, an aldose reductase inhibitor, significantly suppressed the enhancement of iNOS mRNA expression in high glucose concentration. High glucose also significantly increased fibronectin protein production of mesangial cells upon stimulation with LPS plus IFN-γ compared to control glucose. Aminoguanidine reversed this high glucose-induced fibronectin production at dose inhibiting iNOS mRNA expression. Conclusions: These results indicate that high glucose enhances cytokine-induced NO production by rat mesangial cells, and that the activation of PKC and aldose reductase pathway may play a role in this enhancement. In addition, high glucose-induced NO production by the iNOS pathway may promote extracellular matrix accumulation by mesangial cells under certain condition.",
author = "Hyunjin Noh and Hunjoo Ha and Yu, {Mi Ra} and Shin-Wook Kang and Choi, {Kyu Hun} and Han, {Dae Suk} and Lee, {Ho Yung}",
year = "2002",
month = "1",
day = "16",
doi = "10.1159/000046318",
language = "English",
volume = "90",
pages = "78--85",
journal = "Experimental Nephrology",
issn = "0028-2766",
publisher = "S. Karger AG",
number = "1",

}

High glucose increases inducible NO production in cultured rat mesangial cells : Possible role in fibronectin production. / Noh, Hyunjin; Ha, Hunjoo; Yu, Mi Ra; Kang, Shin-Wook; Choi, Kyu Hun; Han, Dae Suk; Lee, Ho Yung.

In: Nephron, Vol. 90, No. 1, 16.01.2002, p. 78-85.

Research output: Contribution to journalArticle

TY - JOUR

T1 - High glucose increases inducible NO production in cultured rat mesangial cells

T2 - Possible role in fibronectin production

AU - Noh, Hyunjin

AU - Ha, Hunjoo

AU - Yu, Mi Ra

AU - Kang, Shin-Wook

AU - Choi, Kyu Hun

AU - Han, Dae Suk

AU - Lee, Ho Yung

PY - 2002/1/16

Y1 - 2002/1/16

N2 - Background/Aim: Increased nitric oxide (NO) generation and action have been suggested to be associated with glomerular hyperfiltration and increased vascular permeability early in diabetes. However, previous studies have primarily focused on the constitutive nitric oxide synthase (cNOS) pathway present in endothelial cells, and the role of the inducible NOS (iNOS) pathway in diabetic nephropathy has remained unclear. This study examined whether high glucose modulates NO synthesis by the iNOS pathway in rat mesangial cells. In addition, the effect of inhibition of the iNOS pathway on fibronectin production was determined to examine the role of the iNOS pathway in high glucose-induced extracellular expansion by mesangial cells. Methods: NO synthesis by the iNOS pathway was evaluated by nitrite and iNOS mRNA and protein productions. The effects of protein kinase C (PKC) inhibitor and aldose reductase inhibitor on the iNOS mRNA expression and aminoguanidine, a relatively specific inhibitor of the iNOS on fibronectin protein production were examined. Results: High 30 mM glucose concentration led to significant increases in nitrite production of rat mesangial cells upon stimulation with lipopolysaccharide (LPS) plus interferon-γ (IFN-γ) compared with control 5.6 mM glucose concentration. Mesangial iNOS mRNA expression and protein production also increased significantly in response to high glucose. The addition of calphostin C, a PKC inhibitor, and 6-bromo-1,3-dioxo-1H-benz[d,e]isoquinoline-2(3H)-acetic acid, an aldose reductase inhibitor, significantly suppressed the enhancement of iNOS mRNA expression in high glucose concentration. High glucose also significantly increased fibronectin protein production of mesangial cells upon stimulation with LPS plus IFN-γ compared to control glucose. Aminoguanidine reversed this high glucose-induced fibronectin production at dose inhibiting iNOS mRNA expression. Conclusions: These results indicate that high glucose enhances cytokine-induced NO production by rat mesangial cells, and that the activation of PKC and aldose reductase pathway may play a role in this enhancement. In addition, high glucose-induced NO production by the iNOS pathway may promote extracellular matrix accumulation by mesangial cells under certain condition.

AB - Background/Aim: Increased nitric oxide (NO) generation and action have been suggested to be associated with glomerular hyperfiltration and increased vascular permeability early in diabetes. However, previous studies have primarily focused on the constitutive nitric oxide synthase (cNOS) pathway present in endothelial cells, and the role of the inducible NOS (iNOS) pathway in diabetic nephropathy has remained unclear. This study examined whether high glucose modulates NO synthesis by the iNOS pathway in rat mesangial cells. In addition, the effect of inhibition of the iNOS pathway on fibronectin production was determined to examine the role of the iNOS pathway in high glucose-induced extracellular expansion by mesangial cells. Methods: NO synthesis by the iNOS pathway was evaluated by nitrite and iNOS mRNA and protein productions. The effects of protein kinase C (PKC) inhibitor and aldose reductase inhibitor on the iNOS mRNA expression and aminoguanidine, a relatively specific inhibitor of the iNOS on fibronectin protein production were examined. Results: High 30 mM glucose concentration led to significant increases in nitrite production of rat mesangial cells upon stimulation with lipopolysaccharide (LPS) plus interferon-γ (IFN-γ) compared with control 5.6 mM glucose concentration. Mesangial iNOS mRNA expression and protein production also increased significantly in response to high glucose. The addition of calphostin C, a PKC inhibitor, and 6-bromo-1,3-dioxo-1H-benz[d,e]isoquinoline-2(3H)-acetic acid, an aldose reductase inhibitor, significantly suppressed the enhancement of iNOS mRNA expression in high glucose concentration. High glucose also significantly increased fibronectin protein production of mesangial cells upon stimulation with LPS plus IFN-γ compared to control glucose. Aminoguanidine reversed this high glucose-induced fibronectin production at dose inhibiting iNOS mRNA expression. Conclusions: These results indicate that high glucose enhances cytokine-induced NO production by rat mesangial cells, and that the activation of PKC and aldose reductase pathway may play a role in this enhancement. In addition, high glucose-induced NO production by the iNOS pathway may promote extracellular matrix accumulation by mesangial cells under certain condition.

UR - http://www.scopus.com/inward/record.url?scp=0036139398&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036139398&partnerID=8YFLogxK

U2 - 10.1159/000046318

DO - 10.1159/000046318

M3 - Article

VL - 90

SP - 78

EP - 85

JO - Experimental Nephrology

JF - Experimental Nephrology

SN - 0028-2766

IS - 1

ER -