Mycophenolate mofetil reduces renal cortical inducible nitric oxide synthase mRNA expression and diminishes glomerulosclerosis in MRL/Ipr mice

Chun Chen Yu, Chih Wei Yang, Mai Szu Wu, Yi Ching Ko, Chiung Tseng Huang, Jenn Jye Hong, Chiu Ching Huang

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Overexpression of inducible nitric oxide synthase (iNOS) has been implicated in the pathogenesis of lupus glomerulonephritis. Mycophenolate mofetil (MMF), a novel immunosuppressive agent, is currently used in organ transplantation and under evaluation for treatment of autoimmune disorders. Mycophenolic acid, the active metabolite of MMF, has been shown to suppress cytokine-induced nitric oxide production in vitro. The aim of this study was to evaluate the effect of MMF on the expression of renal cortical iNOS mRNA and protection against glomerulonephritis in MRL/Ipr mice. Three-month-old MRL/Ipr mice (n = 6) displaying clinical symptoms of glomerulonephritis were treated for 3 months with MMF (90 mg/kg/day) dissolved in a vehicle. Controls were age- and sex-matched mice (n = 6) that received the vehicle alone. By reverse-transcription competitive polymerase chain reaction, we found that the renal cortical iNOS/β-actin mRNA ratio was reduced by 30.8% (P <.05) in MMF-treated mice. Furthermore, MMF significantly reduced urinary nitrite production and degree of glomerulosclerosis. The glomerular volume was reduced by 17.5% (P <.001). Proteinuria was also significantly reduced in the MMF-treated group. However, by electrophoretic mobility shift assay, the nuclear binding of nuclear factor-κB (NF-κB) was not affected by MMF treatment. We conclude that in addition to its immunosuppressive action, MMF may reduce renal cortical iNOS mRNA expression and diminish glomerulosclerosis in MRL/Ipr mice independent of modulation of the NF-κB pathway.

Original languageEnglish
Pages (from-to)69-77
Number of pages9
JournalJournal of Laboratory and Clinical Medicine
Volume138
Issue number1
DOIs
Publication statusPublished - 2001
Externally publishedYes

Fingerprint

Mycophenolic Acid
Nitric Oxide Synthase Type II
Kidney
Messenger RNA
Immunosuppressive Agents
Glomerulonephritis
Transplantation (surgical)
Electrophoretic mobility
Lupus Nephritis
Polymerase chain reaction
Organ Transplantation
Electrophoretic Mobility Shift Assay
Transcription
Metabolites
Nitrites
Proteinuria
Reverse Transcription
Actins
Assays
Nitric Oxide

ASJC Scopus subject areas

  • Medicine(all)
  • Pathology and Forensic Medicine

Cite this

Mycophenolate mofetil reduces renal cortical inducible nitric oxide synthase mRNA expression and diminishes glomerulosclerosis in MRL/Ipr mice. / Yu, Chun Chen; Yang, Chih Wei; Wu, Mai Szu; Ko, Yi Ching; Huang, Chiung Tseng; Hong, Jenn Jye; Huang, Chiu Ching.

In: Journal of Laboratory and Clinical Medicine, Vol. 138, No. 1, 2001, p. 69-77.

Research output: Contribution to journalArticle

Yu, Chun Chen ; Yang, Chih Wei ; Wu, Mai Szu ; Ko, Yi Ching ; Huang, Chiung Tseng ; Hong, Jenn Jye ; Huang, Chiu Ching. / Mycophenolate mofetil reduces renal cortical inducible nitric oxide synthase mRNA expression and diminishes glomerulosclerosis in MRL/Ipr mice. In: Journal of Laboratory and Clinical Medicine. 2001 ; Vol. 138, No. 1. pp. 69-77.
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