The novel NF-κB activation inhibitor dehydroxymethyl-epoxyquinomicin suppresses anti-thy1.1-induced glomerulonephritis in rats

Takeo Kosaka, Akira Miyajima, Eiji Kikuchi, Yutaka Horiguchi, Kazuo Umezawa, Takashi Ohigashi, Jun Nakashima, Tomohiko Asano, Mototsugu Oya

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Background: NF-κB participates in the transcriptional regulation of numerous genes, and many studies have confirmed the activation of NF-κB in inflammatory renal diseases. Therefore, NF-κB is a promising target for the treatment of these diseases. We tested the effects of dehydroxymethyl- epoxyquinomicin (DHMEQ), a novel NF-κB activation inhibitor, on anti-thy1.1 antibody-induced glomerulonephritis (Thy1.1 GN). Methods: Thy1.1 GN was induced in Sprague-Dawley rats (6/group) by intravenous injection of anti-thy 1.1 antibody. The effects of DHMEQ (8 mg/kg/day) on the glomerular disease were evaluated using periodic acid-Schiff and Masson trichrome stains, immunohistochemistry for proliferating cell nuclear antigen, fibronectin and CD45 (leukocyte common antigen) and TUNEL staining. NF-κB activation was analyzed by a fluorescent electrophoretic mobility shift assay. Results: On day 7, DHMEQ treatment resulted in marked inhibition of NF-κB, decreased proteinuria (223.2 ± 42.3 vs. 434.8 ± 16.5 mg/kg/day, p < 0.05), preserved creatinine clearance (1.93 ± 0.38 vs. 1.07 ± 0.29 l/day, p < 0.01), decreased glomerular cell proliferation (15.8 ± 1.2 vs. 31.2 ± 0.8 nuclei/glomerular cross-section) and mesangial matrix deposition, and an increase in glomerular and tubular apoptosis without inducing any obvious adverse effects. Conclusion: DHMEQ inhibited NF-κB and thereby suppressed the inflammatory renal responses in rats with Thy1.1 GN.

Original languageEnglish
JournalNephron - Experimental Nephrology
Volume110
Issue number1
DOIs
Publication statusPublished - 2008 Sep

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Glomerulonephritis
CD45 Antigens
Kidney
Periodic Acid
Antibodies
In Situ Nick-End Labeling
Proliferating Cell Nuclear Antigen
Electrophoretic Mobility Shift Assay
Proteinuria
Fibronectins
Intravenous Injections
Sprague Dawley Rats
Anti-Idiotypic Antibodies
Creatinine
Immunohistochemistry
Cell Proliferation
Apoptosis
Staining and Labeling
Therapeutics
Genes

Keywords

  • Apoptosis
  • Crescent formation
  • Leukocyte migration
  • Nuclear factor-B
  • Proliferating cell nuclear antigen
  • Thy-1 model

ASJC Scopus subject areas

  • Nephrology
  • Physiology
  • Genetics
  • Medicine(all)

Cite this

The novel NF-κB activation inhibitor dehydroxymethyl-epoxyquinomicin suppresses anti-thy1.1-induced glomerulonephritis in rats. / Kosaka, Takeo; Miyajima, Akira; Kikuchi, Eiji; Horiguchi, Yutaka; Umezawa, Kazuo; Ohigashi, Takashi; Nakashima, Jun; Asano, Tomohiko; Oya, Mototsugu.

In: Nephron - Experimental Nephrology, Vol. 110, No. 1, 09.2008.

Research output: Contribution to journalArticle

Kosaka, Takeo ; Miyajima, Akira ; Kikuchi, Eiji ; Horiguchi, Yutaka ; Umezawa, Kazuo ; Ohigashi, Takashi ; Nakashima, Jun ; Asano, Tomohiko ; Oya, Mototsugu. / The novel NF-κB activation inhibitor dehydroxymethyl-epoxyquinomicin suppresses anti-thy1.1-induced glomerulonephritis in rats. In: Nephron - Experimental Nephrology. 2008 ; Vol. 110, No. 1.
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abstract = "Background: NF-κB participates in the transcriptional regulation of numerous genes, and many studies have confirmed the activation of NF-κB in inflammatory renal diseases. Therefore, NF-κB is a promising target for the treatment of these diseases. We tested the effects of dehydroxymethyl- epoxyquinomicin (DHMEQ), a novel NF-κB activation inhibitor, on anti-thy1.1 antibody-induced glomerulonephritis (Thy1.1 GN). Methods: Thy1.1 GN was induced in Sprague-Dawley rats (6/group) by intravenous injection of anti-thy 1.1 antibody. The effects of DHMEQ (8 mg/kg/day) on the glomerular disease were evaluated using periodic acid-Schiff and Masson trichrome stains, immunohistochemistry for proliferating cell nuclear antigen, fibronectin and CD45 (leukocyte common antigen) and TUNEL staining. NF-κB activation was analyzed by a fluorescent electrophoretic mobility shift assay. Results: On day 7, DHMEQ treatment resulted in marked inhibition of NF-κB, decreased proteinuria (223.2 ± 42.3 vs. 434.8 ± 16.5 mg/kg/day, p < 0.05), preserved creatinine clearance (1.93 ± 0.38 vs. 1.07 ± 0.29 l/day, p < 0.01), decreased glomerular cell proliferation (15.8 ± 1.2 vs. 31.2 ± 0.8 nuclei/glomerular cross-section) and mesangial matrix deposition, and an increase in glomerular and tubular apoptosis without inducing any obvious adverse effects. Conclusion: DHMEQ inhibited NF-κB and thereby suppressed the inflammatory renal responses in rats with Thy1.1 GN.",
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AU - Kosaka, Takeo

AU - Miyajima, Akira

AU - Kikuchi, Eiji

AU - Horiguchi, Yutaka

AU - Umezawa, Kazuo

AU - Ohigashi, Takashi

AU - Nakashima, Jun

AU - Asano, Tomohiko

AU - Oya, Mototsugu

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N2 - Background: NF-κB participates in the transcriptional regulation of numerous genes, and many studies have confirmed the activation of NF-κB in inflammatory renal diseases. Therefore, NF-κB is a promising target for the treatment of these diseases. We tested the effects of dehydroxymethyl- epoxyquinomicin (DHMEQ), a novel NF-κB activation inhibitor, on anti-thy1.1 antibody-induced glomerulonephritis (Thy1.1 GN). Methods: Thy1.1 GN was induced in Sprague-Dawley rats (6/group) by intravenous injection of anti-thy 1.1 antibody. The effects of DHMEQ (8 mg/kg/day) on the glomerular disease were evaluated using periodic acid-Schiff and Masson trichrome stains, immunohistochemistry for proliferating cell nuclear antigen, fibronectin and CD45 (leukocyte common antigen) and TUNEL staining. NF-κB activation was analyzed by a fluorescent electrophoretic mobility shift assay. Results: On day 7, DHMEQ treatment resulted in marked inhibition of NF-κB, decreased proteinuria (223.2 ± 42.3 vs. 434.8 ± 16.5 mg/kg/day, p < 0.05), preserved creatinine clearance (1.93 ± 0.38 vs. 1.07 ± 0.29 l/day, p < 0.01), decreased glomerular cell proliferation (15.8 ± 1.2 vs. 31.2 ± 0.8 nuclei/glomerular cross-section) and mesangial matrix deposition, and an increase in glomerular and tubular apoptosis without inducing any obvious adverse effects. Conclusion: DHMEQ inhibited NF-κB and thereby suppressed the inflammatory renal responses in rats with Thy1.1 GN.

AB - Background: NF-κB participates in the transcriptional regulation of numerous genes, and many studies have confirmed the activation of NF-κB in inflammatory renal diseases. Therefore, NF-κB is a promising target for the treatment of these diseases. We tested the effects of dehydroxymethyl- epoxyquinomicin (DHMEQ), a novel NF-κB activation inhibitor, on anti-thy1.1 antibody-induced glomerulonephritis (Thy1.1 GN). Methods: Thy1.1 GN was induced in Sprague-Dawley rats (6/group) by intravenous injection of anti-thy 1.1 antibody. The effects of DHMEQ (8 mg/kg/day) on the glomerular disease were evaluated using periodic acid-Schiff and Masson trichrome stains, immunohistochemistry for proliferating cell nuclear antigen, fibronectin and CD45 (leukocyte common antigen) and TUNEL staining. NF-κB activation was analyzed by a fluorescent electrophoretic mobility shift assay. Results: On day 7, DHMEQ treatment resulted in marked inhibition of NF-κB, decreased proteinuria (223.2 ± 42.3 vs. 434.8 ± 16.5 mg/kg/day, p < 0.05), preserved creatinine clearance (1.93 ± 0.38 vs. 1.07 ± 0.29 l/day, p < 0.01), decreased glomerular cell proliferation (15.8 ± 1.2 vs. 31.2 ± 0.8 nuclei/glomerular cross-section) and mesangial matrix deposition, and an increase in glomerular and tubular apoptosis without inducing any obvious adverse effects. Conclusion: DHMEQ inhibited NF-κB and thereby suppressed the inflammatory renal responses in rats with Thy1.1 GN.

KW - Apoptosis

KW - Crescent formation

KW - Leukocyte migration

KW - Nuclear factor-B

KW - Proliferating cell nuclear antigen

KW - Thy-1 model

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