| Myocardial knockdown of mRNA-stabilizing protein HuR attenuates post-MI inflammatory response and left ventricular dysfunction in IL-10-null mice. | |
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MedLine Citation:
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PMID: 20219984 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Prolonged inflammatory response is associated with left ventricular (LV) dysfunction and adverse remodeling following myocardial infarction (MI). IL-10 inhibits inflammation by suppressing HuR-mediated mRNA stabilization of proinflammatory cytokines. Here we report that following MI, IL-10(-/-) mice showed exaggerated LV dysfunction, fibrosis, and cardiomyocyte apoptosis. Short-hairpin RNA (shRNA)-mediated knockdown of HuR in the myocardium significantly reversed MI-induced LV dysfunctions and LV remodeling. HuR knockdown significantly reduced MI-induced cardiomyocyte apoptosis concomitant with reduced p53 expression. Moreover, HuR knockdown significantly reduced infarct size and fibrosis area, which in turn was associated with decreased TGF-beta expression. In vitro, stable knockdown of HuR in mouse macrophage cell line RAW 264.7 corroborated in vivo data and revealed reduced mRNA expression of TNF-alpha, TGF-beta, and p53 following LPS challenge, which was associated with a marked reduction in the mRNA stability of these genes. Taken together, our studies suggest that HuR is a direct target of IL-10, and HuR knockdown mimics anti-inflammatory effects of IL-10. |
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Authors:
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Prasanna Krishnamurthy; Erin Lambers; Suresh Verma; Tina Thorne; Gangjian Qin; Douglas W Losordo; Raj Kishore |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-03-10 |
Journal Detail:
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Title: FASEB journal : official publication of the Federation of American Societies for Experimental Biology Volume: 24 ISSN: 1530-6860 ISO Abbreviation: FASEB J. Publication Date: 2010 Jul |
Date Detail:
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Created Date: 2010-07-01 Completed Date: 2010-08-03 Revised Date: 2012-03-08 |
Medline Journal Info:
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Nlm Unique ID: 8804484 Medline TA: FASEB J Country: United States |
Other Details:
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Languages: eng Pagination: 2484-94 Citation Subset: IM |
Affiliation:
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Feinberg Cardiovascular Research Institute, Division of Cardiology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA. p-krishnamurthy@northwestern.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antigens, Surface / genetics*, physiology Cell Line Inflammation / etiology, prevention & control* Interleukin-10 / deficiency*, physiology Macrophages Mice Mice, Knockout Myocardial Infarction / pathology* Myocardium / metabolism, pathology* RNA Stability RNA, Small Interfering / pharmacology RNA-Binding Proteins / genetics*, physiology Ventricular Dysfunction, Left / prevention & control* |
| Grant Support | |
ID/Acronym/Agency:
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AA014575/AA/NIAAA NIH HHS; HL091983/HL/NHLBI NIH HHS; R01 HL053354-08/HL/NHLBI NIH HHS; R01 HL053354-09/HL/NHLBI NIH HHS; R01 HL053354-10/HL/NHLBI NIH HHS; R01 HL053354-11A2/HL/NHLBI NIH HHS; R01 HL053354-12/HL/NHLBI NIH HHS; R01 HL080137-01A1/HL/NHLBI NIH HHS; R01 HL080137-02/HL/NHLBI NIH HHS; R01 HL080137-03/HL/NHLBI NIH HHS; R01 HL080137-04/HL/NHLBI NIH HHS; R01 HL080137-05/HL/NHLBI NIH HHS; R01 HL091983-01A1/HL/NHLBI NIH HHS; R01 HL091983-03/HL/NHLBI NIH HHS; R01 HL091983-04/HL/NHLBI NIH HHS; R01 HL093439-02/HL/NHLBI NIH HHS; R01 HL095874-01/HL/NHLBI NIH HHS; R01 HL095874-02/HL/NHLBI NIH HHS; R01 HL095874-03/HL/NHLBI NIH HHS; R01 HL095874-04/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antigens, Surface; 0/ELAVL1 protein, human; 0/RNA, Small Interfering; 0/RNA-Binding Proteins; 130068-27-8/Interleukin-10 |
| Comments/Corrections | |
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