Effects of Inosine Monophosphate Dehydrogenase Inhibition on High Glucose-Induced Cellular Reactive Oxygen Species in Mesangial Cells

J. S. Song, K. H. Huh, J. Park, M. K. Ju, M. S. Kim, YuSeun Kim

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Mesangial cell extracellular matrix (ECM) synthesis plays an important role in chronic renal diseases including chronic renal allograft dysfunction and diabetic nephropathy. Although inosine monophosphate dehydrogenase 2 (IMPDH2), as a target of mycophenolic acid (MPA), is important for de novo guanosine synthesis in lymphocytes, mesenchymal cells are not wholly dependent on it. To explore the importance of IMPDH2 on the inhibitory effects of MPA in mesangial cells (MC), we compared the effects of MPA and IMPDH2 siRNA on high glucose (HG)-induced fibronectin secretion and cellular reactive oxygen species (ROS). Mouse mesangial cells (MMC) were stimulated with HG (30 mmol/L D-glucose) in the presence or absence of MPA pretreatment or IMPDH2 siRNA transfection. Fibronectin secretion was measured by Western blot analysis, and dichlorofluorescein (DCF)-sensitive cellular ROS assessed by flow cytometry. HG increased fibronectin secretion by 1.8-fold at 24 hours and DCF-sensitive cellular ROS by 1.5-fold at 1 hour. MPA at 10 μmol/L totally inhibited HG-induced fibronectin secretion and cellular ROS in MMC. However, IMPDH2 siRNA only partially suppressed HG-induced fibronectin secretion and cellular ROS. These results suggested that MPA may inhibit HG-induced fibronectin secretion partially through inhibiting cellular ROS and the inhibition of IMPDH2 may be partially involved in the mechanism of MPA.

Original languageEnglish
Pages (from-to)464-466
Number of pages3
JournalTransplantation Proceedings
Volume40
Issue number2
DOIs
Publication statusPublished - 2008 Mar 1

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Mycophenolic Acid
Inosine Monophosphate
Mesangial Cells
Reactive Oxygen Species
Fibronectins
Oxidoreductases
Glucose
Small Interfering RNA
Glomerular Mesangium
Guanosine
Diabetic Nephropathies
Chronic Renal Insufficiency
Transfection
Allografts
Flow Cytometry
Western Blotting
Lymphocytes
Kidney

All Science Journal Classification (ASJC) codes

  • Surgery
  • Transplantation

Cite this

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abstract = "Mesangial cell extracellular matrix (ECM) synthesis plays an important role in chronic renal diseases including chronic renal allograft dysfunction and diabetic nephropathy. Although inosine monophosphate dehydrogenase 2 (IMPDH2), as a target of mycophenolic acid (MPA), is important for de novo guanosine synthesis in lymphocytes, mesenchymal cells are not wholly dependent on it. To explore the importance of IMPDH2 on the inhibitory effects of MPA in mesangial cells (MC), we compared the effects of MPA and IMPDH2 siRNA on high glucose (HG)-induced fibronectin secretion and cellular reactive oxygen species (ROS). Mouse mesangial cells (MMC) were stimulated with HG (30 mmol/L D-glucose) in the presence or absence of MPA pretreatment or IMPDH2 siRNA transfection. Fibronectin secretion was measured by Western blot analysis, and dichlorofluorescein (DCF)-sensitive cellular ROS assessed by flow cytometry. HG increased fibronectin secretion by 1.8-fold at 24 hours and DCF-sensitive cellular ROS by 1.5-fold at 1 hour. MPA at 10 μmol/L totally inhibited HG-induced fibronectin secretion and cellular ROS in MMC. However, IMPDH2 siRNA only partially suppressed HG-induced fibronectin secretion and cellular ROS. These results suggested that MPA may inhibit HG-induced fibronectin secretion partially through inhibiting cellular ROS and the inhibition of IMPDH2 may be partially involved in the mechanism of MPA.",
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Effects of Inosine Monophosphate Dehydrogenase Inhibition on High Glucose-Induced Cellular Reactive Oxygen Species in Mesangial Cells. / Song, J. S.; Huh, K. H.; Park, J.; Ju, M. K.; Kim, M. S.; Kim, YuSeun.

In: Transplantation Proceedings, Vol. 40, No. 2, 01.03.2008, p. 464-466.

Research output: Contribution to journalArticle

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