| Direct targeting of fibroblast growth factor-inducible 14 protein protects against renal ischemia reperfusion injury. | |
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MedLine Citation:
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PMID: 20927042 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is known to have pivotal roles in various inflammatory processes. The TWEAK receptor, fibroblast growth factor-inducible 14 (Fn14), has various unique functions under physiological and pathological conditions; however, the therapeutic potential of its direct targeting remains unknown. Here, we found that Fn14 expression was highly upregulated in ischemic renal tissues and tubular epithelial cells of patient biopsies and experimental animal models of renal injury. To clarify the function of Fn14 in ischemia reperfusion injury, we coincubated renal tubular cells with ITEM-2, an anti-Fn14 blocking monoclonal antibody, and found that it inhibited the production of proinflammatory cytokines and chemokines after injury. Furthermore, Fn14 blockade downregulated the local expression of several proinflammatory mediators, reduced accumulation of neutrophils and macrophages in ischemic tissues, and inhibited tubular cell apoptosis. Importantly, Fn14 blockade attenuated the development of chronic fibrosis after ischemia reperfusion injury and significantly prolonged the survival of lethally injured mice. Thus, we conclude that Fn14 is a critical mediator in the pathogenesis of ischemia reperfusion injury. |
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Authors:
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Kiyohiko Hotta; Masayuki Sho; Ichiro Yamato; Keiji Shimada; Hiroshi Harada; Takahiro Akahori; Shinji Nakamura; Noboru Konishi; Hideo Yagita; Katsuya Nonomura; Yoshiyuki Nakajima |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-10-06 |
Journal Detail:
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Title: Kidney international Volume: 79 ISSN: 1523-1755 ISO Abbreviation: Kidney Int. Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2010-12-30 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0323470 Medline TA: Kidney Int Country: United States |
Other Details:
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Languages: eng Pagination: 179-88 Citation Subset: IM |
Affiliation:
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Department of Surgery, Nara Medical University, Nara, Japan. |
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| Comments/Corrections | |
Comment In:
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Kidney Int. 2011 Jan;79(2):151-3
[PMID:
21191390
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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