Complete Disruption of All Nitric Oxide Synthase Genes Causes Markedly Accelerated Renal Lesion Formation Following Unilateral Ureteral Obstruction in Mice In Vivo
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- Morisada Naoya
- Department of Pediatrics, School of Medicine, University of Occupational and Environmental Health, Japan
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- Nomura Masayoshi
- Department of Urology, School of Medicine, University of Occupational and Environmental Health, Japan
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- Nishii Hisae
- Department of Urology, School of Medicine, University of Occupational and Environmental Health, Japan
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- Furuno Yumi
- Department of Pharmacology, School of Medicine, University of Occupational and Environmental Health, Japan
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- Sakanashi Mayuko
- Department of Pharmacology, Graduate School of Medicine, University of the Ryukyus, Japan
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- Sabanai Ken
- Department of Pharmacology, School of Medicine, University of Occupational and Environmental Health, Japan
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- Toyohira Yumiko
- Department of Pharmacology, School of Medicine, University of Occupational and Environmental Health, Japan
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- Ueno Susumu
- Department of Pharmacology, School of Medicine, University of Occupational and Environmental Health, Japan
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- Watanabe Seiji
- Department of Pediatrics, School of Medicine, University of Occupational and Environmental Health, Japan
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- Tamura Masahito
- Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Japan
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- Matsumoto Tetsuro
- Department of Urology, School of Medicine, University of Occupational and Environmental Health, Japan
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- Tanimoto Akihide
- Department of Pathology, Kagoshima University Graduate School of Medical and Dental Sciences, Japan
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- Sasaguri Yasuyuki
- Department of Pathology, School of Medicine, University of Occupational and Environmental Health, Japan
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- Shimokawa Hiroaki
- Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Japan
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- Kusuhara Koichi
- Department of Pediatrics, School of Medicine, University of Occupational and Environmental Health, Japan
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- Yanagihara Nobuyuki
- Department of Pharmacology, School of Medicine, University of Occupational and Environmental Health, Japan
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- Shirahata Akira
- Department of Pediatrics, School of Medicine, University of Occupational and Environmental Health, Japan
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- Tsutsui Masato
- Department of Pharmacology, School of Medicine, University of Occupational and Environmental Health, Japan Department of Pharmacology, Graduate School of Medicine, University of the Ryukyus, Japan
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説明
The role of nitric oxide (NO) derived from all three NO synthases (NOSs) in renal lesion formation remains to be fully elucidated. We addressed this point in mice lacking all NOSs. Renal injury was induced by unilateral ureteral obstruction (UUO). UUO caused significant renal lesion formation (tubular apoptosis, interstitial fibrosis, and glomerulosclerosis) in wild-type, singly, and triply NOS−/− mice. However, the extents of renal lesion formation were markedly and most accelerated in the triply NOS−/− genotype. UUO also elicited the infiltration of inflammatory macrophages, up-regulation of transforming growth factor (TGF)-β1, and induction of epithelial mesenchymal transition (EMT) in all of the genotypes; however, the extents were again largest by far in the triply NOS−/− genotype. Importantly, long-term treatment with the angiotensin II type 1 (AT1)-receptor blocker olmesartan significantly prevented the exacerbation of those renal structural changes after UUO in the triply NOS−/− genotype, along with amelioration of the macrophage infiltration, TGF-β1 levels, and EMT. These results provide the first evidence that the complete disruption of all NOS genes results in markedly accelerated renal lesion formation in response to UUO in mice in vivo through the AT1-receptor pathway, demonstrating the critical renoprotective role of all NOSs-derived NO against pathological renal remodeling.
収録刊行物
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- Journal of Pharmacological Sciences
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Journal of Pharmacological Sciences 114 (4), 379-389, 2010
公益社団法人 日本薬理学会
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詳細情報 詳細情報について
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- CRID
- 1390282680157484672
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- NII論文ID
- 10029890896
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- NII書誌ID
- AA11806667
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- ISSN
- 13478648
- 13478613
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- NDL書誌ID
- 10926413
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
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