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SIRT2 Regulates LPS-Induced Renal Tubular CXCL2 and CCL2 Expression.
MedLine Citation:
PMID:  25349202     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Sirtuin 2 (SIRT2), a NAD(+)-dependent histone deacetylase, is involved in carcinogenesis and genomic instability and modulates proinflammatory immune responses. However, its role in renal inflammatory injury has not been demonstrated. In this study, we explored the expression patterns of CXCL2 and CCL2 in kidney tissue from Sirt2(-/-) and Sirt2(+/+) mice and in mouse proximal tubular epithelial (MPT) cells. CXCL2 and CCL2 were significantly downregulated at both the mRNA and the protein levels in kidneys of LPS-treated Sirt2(-/-) mice compared with those of LPS-treated Sirt2(+/+) mice. Furthermore, SIRT2 deficiency ameliorated LPS-induced infiltration of neutrophils and macrophages, acute tubular injury, and decrease of renal function. Supporting these observations, CXCL2 and CCL2 expression levels were lower in MPT cells treated with SIRT2-siRNA than in cells treated with control-siRNA, and adenovirus-mediated overexpression of SIRT2 in MPT cells significantly increased the LPS-induced expression of CXCL2 and CCL2 at the mRNA and protein levels. In addition, SIRT2 interacted with mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1), and SIRT2-knockdown increased the acetylation of MKP-1 and suppressed the phosphorylation of p38 MAPK and c-Jun N-terminal kinase in LPS-treated MPT cells. SIRT2 also regulated p65 binding to the promoters of CXCL2 and CCL2. Taken together, these findings indicate that SIRT2 is associated with expression of renal CXCL2 and CCL2 and that regulation of SIRT2 might be an important therapeutic target for renal inflammatory injury.
Authors:
Yu Jin Jung; Ae Sin Lee; Tung Nguyen-Thanh; Dal Kim; Kyung Pyo Kang; Sik Lee; Sung Kwang Park; Won Kim
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-10-27
Journal Detail:
Title:  Journal of the American Society of Nephrology : JASN     Volume:  -     ISSN:  1533-3450     ISO Abbreviation:  J. Am. Soc. Nephrol.     Publication Date:  2014 Oct 
Date Detail:
Created Date:  2014-10-28     Completed Date:  -     Revised Date:  2014-10-29    
Medline Journal Info:
Nlm Unique ID:  9013836     Medline TA:  J Am Soc Nephrol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2014 by the American Society of Nephrology.
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