| Klotho protects against mouse renal fibrosis by inhibiting Wnt signaling. | |
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MedLine Citation:
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PMID: 23034937 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Augmented Wnt signaling has been implicated in many fibrotic diseases including obstructive nephropathy. Soluble form Klotho has been reported to function as a secreted Wnt antagonist. In this study, we tested whether Klotho protein could reduce renal fibrosis by inhibition of Wnt signaling. Transgenic mice that overexpressed Klotho, wild-type mice, and Klotho hetero mutant mice underwent unilateral ureteral obstruction (UUO). In some Klotho hetero mutant mice, Klotho-encoding plasmid was transferred into the skeletal muscle by electroporation. UUO induced activation of Wnt signaling in wild-type but less in Klotho transgenic mice. Enhanced tubulointerstitial fibrosis in wild-type mice was also attenuated in Klotho transgenic mice. In contrast, Wnt signaling and concomitant tubulointerstitial fibrosis were further augmented in Klotho hetero mutant mice after UUO compared with wild-type mice. In Klotho-encoding plasmid-transfected Klotho hetero mutant mice, however, Wnt signaling was markedly reduced accompanied by a decrease in extracellular matrix deposition after UUO. In vitro studies showed that stimulation of Wnt3a induced prolonged cell cycle arrest at G(2)/M phase, with a resultant increase in production of fibrogenic cytokines. Cotreatment with Klotho bypassed the G(2)/M arrest and reduced fibrogenic cytokine production. In conclusion, Klotho is a critical negative regulator of Wnt signaling and a suppressor of renal fibrosis in the obstructed kidney model. |
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Authors:
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Minoru Satoh; Hajime Nagasu; Yoshitaka Morita; Terry P Yamaguchi; Yashpal S Kanwar; Naoki Kashihara |
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Publication Detail:
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Type: In Vitro; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2012-10-03 |
Journal Detail:
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Title: American journal of physiology. Renal physiology Volume: 303 ISSN: 1522-1466 ISO Abbreviation: Am. J. Physiol. Renal Physiol. Publication Date: 2012 Dec |
Date Detail:
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Created Date: 2012-12-17 Completed Date: 2013-04-02 Revised Date: 2013-05-14 |
Medline Journal Info:
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Nlm Unique ID: 100901990 Medline TA: Am J Physiol Renal Physiol Country: United States |
Other Details:
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Languages: eng Pagination: F1641-51 Citation Subset: IM |
Affiliation:
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Dept. of Nephrology and Hypertension, Kawasaki Medical School, Kurashiki, Okayama Japan. msatoh@med.kawasaki-m.ac.jp |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Cycle / physiology Cells, Cultured Disease Models, Animal Female Fibrosis Glucuronidase / genetics, physiology* Kidney / pathology*, physiopathology Kidney Diseases / pathology, physiopathology, prevention & control* Male Mice Mice, Mutant Strains Mice, Transgenic Plasmids Transfection Ureteral Obstruction / complications*, pathology, physiopathology Wnt Signaling Pathway / physiology* |
| Grant Support | |
ID/Acronym/Agency:
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DK-60635/DK/NIDDK NIH HHS; R01 DK060635/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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EC 3.2.1.31/Glucuronidase; EC 3.2.1.31/klotho protein |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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