Microarray Analysis of Glomerular Gene Expression in Murine Lupus Nephritis
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概要
- 論文の詳細を見る
To elucidate the molecular mechanism of glomerular events in lupus nephritis, we performed genome-wide mRNA expression analysis of glomeruli microdissected from lupus mice. MRL/lpr mice (12-week-old) were orally given vehicle or prednisolone (10 mg/kg per day) for 4 weeks. Renal histology of MRL/lpr mice revealed mesangial proliferative glomerulonephritis with cellular infiltration of macrophages, T cells, and neutrophils. We identified 567 up-regulated genes in MRL/lpr glomeruli compared to control congenic mice. Those included complement components, adhesion molecules, chemokines and their receptors, and molecules related to antigen presentation. Over 130 genes were considered preferentially or exclusively expressed in hematopoietic cell lineages possibly reflecting leukocytes accumulation. Of note is the finding that chemokines and chemokine receptors (CCL3, CCL4, CCL5, CXCL9, CXCL10, CXCL11, CXCL16, CCR5, CXCR3, and CXCR6) that are related to T helper 1 (Th1) cells accumulation were up-regulated concomitantly with increased expression of Ebi3, a subunit of IL-27 that plays a role in Th1 predominance. These changes were accompanied by increased mRNA expression of many genes that were inducible by Th1 cytokine interferon-γ. Prednisolone markedly attenuated glomerular lesion and leukocyte influx parallel with the reduction of enhanced gene expression. The present study shows additional evidence supporting glomerular Th1 cells accumulation and their role. Our data also provide an important resource in seeking new therapeutic targets to lupus nephritis.
- 社団法人 日本薬理学会の論文
- 2008-01-20
著者
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Miura Katsuyuki
Department of Health Science, Shiga University of Medical Science
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Inoue Hiroko
Division Of Cardiology Sakurabashi Watanabe Hospital
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Iwao H
Department Of Pharmacology Osaka City University Medical School
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IWAO Hiroshi
Department of Pharmacology, Osaka City University School of Medicine
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Inanami Hitoshi
大阪掖済会病院 循環器
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Iwao Hiroshi
大阪市立大学 医学部薬効安全性学
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Sato Hiroshi
Department Of Pharmacology Osaka City University Medical School
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Iwao Hiroshi
大阪市立大学 医分子生体医学
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Miura Katsuyuki
Department Of Applied Pharmacology And Therapeutics Osaka City University Medical School
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Miura Katsuyuki
大阪市立大学 医分子生体医学
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Miura Katsuyuki
大阪市立大学 薬理
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Okumura M
Ohno Memorial Hospital
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Okumura Michiaki
大阪市立総合医療センター 内科
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Okumura Michiaki
大阪市立大学 薬理
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Miura K
Applied Pharmacology And Therapeutics Osaka City University Medical School
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Iwai Tomoaki
Department Of Applied Pharmacology And Therapeutics Osaka City University Medical School
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TERAMOTO Kae
Department of Applied Pharmacology and Therapeutics, Osaka City University Medical School
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NEGORO Nobuo
Department of Clinical Immunology, Osaka City University Medical School
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KITAMOTO Kouichirou
Department of Applied Pharmacology and Therapeutics, Osaka City University Medical School
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OKAMURA Mikio
Ohno Memorial Hospital
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Teramoto Kae
Department Of Applied Pharmacology And Therapeutics Osaka City University Medical School
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Negoro Nobuo
Department Of Clinical Immunology Osaka City University Medical School
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Iwao Hiroshi
Department Of Pharmacology Graduate School Of Medicine Osaka City University
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Kitamoto Kouichirou
Department Of Applied Pharmacology And Therapeutics Osaka City University Medical School
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Iwao Hiroshi
Department Of Cardiovascular Medicine Akita University Graduate School Of Medicine
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