ReferenceID 174
The inflammatory cytokines TWEAK and TNFα reduce renal klotho expression through NFκB
J Am Soc Nephrol
Proinflammatory cytokines contribute to renal injury, but the downstream effectors within kidney cells are not well understood. One candidate effector is Klotho, a protein expressed by renal cells that has antiaging pro
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Record Fields
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- Reference Id
- 174
- Evidence Id
- 16764
- Core Evidence Id
- 16764
- Source Reference Id
- 310
- Herb2 Reference Id
- HBREF000571
- Subject Paper Key
- HBIN038876_21719790
- Pubmed Id
- 21719790
- Doi
- 10.1681/ASN.2010101073
- Paper Title
- The inflammatory cytokines TWEAK and TNFα reduce renal klotho expression through NFκB
- Paper Abstract
- Proinflammatory cytokines contribute to renal injury, but the downstream effectors within kidney cells are not well understood. One candidate effector is Klotho, a protein expressed by renal cells that has antiaging properties; Klotho-deficient mice have an accelerated aging-like phenotype, including vascular injury and renal injury. Whether proinflammatory cytokines, such as TNF and TNF-like weak inducer of apoptosis (TWEAK), modulate Klotho is unknown. In mice, exogenous administration of TWEAK decreased expression of Klotho in the kidney. In the setting of acute kidney injury induced by folic acid, the blockade or absence of TWEAK abrogated the injury-related decrease in renal and plasma Klotho levels. TWEAK, TNFα, and siRNA-mediated knockdown of IκBα all activated NFκB and reduced Klotho expression in the MCT tubular cell line. Furthermore, inhibition of NFκB with parthenolide prevented TWEAK- or TNFα-induced downregulation of Klotho. Inhibition of histone deacetylase reversed TWEAK-induced downregulation of Klotho, and chromatin immunoprecipitation showed that TWEAK promotes RelA binding to the Klotho promoter, inducing its deacetylation. In conclusion, inflammatory cytokines, such as TWEAK and TNFα, downregulate Klotho expression through an NFκB-dependent mechanism. These results may partially explain the relationship between inflammation and diseases characterized by accelerated aging of organs, including CKD.
- Journal
- J Am Soc Nephrol
- Publish Year
- 2011
- Experiment Subject
- klotho-deficient mice
- Experiment Type
- Animal Experiment
- Phenotype Related
- Paper Title Cn
- Paper Title En
- The inflammatory cytokines TWEAK and TNFα reduce renal klotho expression through NFκB
- Bilingual Status
- semi_complete