Document Detail


CD247 modulates blood pressure by altering T-lymphocyte infiltration in the kidney.
MedLine Citation:
PMID:  24343121     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The CD3 ζ chain (CD247), a gene involved in T-cell signaling, has been shown to associate with blood pressure in human genetic studies. To test the functional role of CD247 in hypertension and renal disease, zinc-finger nucleases targeting CD247 were injected into Dahl salt-sensitive (SS/JrHsdMcwi) embryos. The resulting 11-bp frameshift deletion in exon 1 of CD247 led to a predicted premature stop codon. Western blotting confirmed the absence of CD247 protein in the thymus, and flow cytometry (n=5-9 per group) demonstrated that the mutant rats (CD247(-/-)) have a >99% reduction in circulating CD3(+) T cells compared with littermate controls (CD247(+/+)). Studies were performed on age-matched, littermate male, CD247(+/+) and CD247(-/-) rats fed a 4.0% NaCl diet for 3 weeks. The infiltration of CD3(+) T cells into the kidney after high salt was significantly blunted in CD247(-/-) (1.4±0.4×10(5) cells per kidney) when compared with that in the CD247(+/+) (8.7±2.0×10(5) cells per kidney). Accompanying the reduced infiltration of T cells, mean arterial blood pressure was significantly lower in CD247(-/-) than in CD247(+/+) (134±1 versus 151±2 mm Hg). As an index of kidney disease, urinary albumin and protein excretion rates were significantly reduced in CD247(-/-) (17±1 and 62±2 mg/d, respectively) when compared with that in CD247(+/+) (49±3 and 121±5 mg/d, respectively). Glomerular and renal tubular damage were also attenuated in the CD247(-/-). These studies demonstrate that functional T cells are required for the full development of Dahl salt-sensitive hypertension and indicate that the association between CD247 and hypertension in humans may be related to altered immune cell function.
Authors:
Nathan Rudemiller; Hayley Lund; Howard J Jacob; Aron M Geurts; David L Mattson;
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2013-12-16
Journal Detail:
Title:  Hypertension     Volume:  63     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2014 Mar 
Date Detail:
Created Date:  2014-02-13     Completed Date:  2014-04-15     Revised Date:  2014-05-12    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  559-64     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigens, CD3 / genetics*,  metabolism
Blotting, Western
Disease Models, Animal
Gene Expression Regulation*
Hypertension / genetics*,  immunology,  metabolism
Immunity, Cellular / genetics*
Kidney / immunology,  metabolism,  pathology*
Male
RNA / genetics*
Rats
Rats, Inbred Dahl
Real-Time Polymerase Chain Reaction
T-Lymphocytes / immunology*,  metabolism,  pathology
Grant Support
ID/Acronym/Agency:
DK-96859/DK/NIDDK NIH HHS; HL116264/HL/NHLBI NIH HHS; P01 HL029587/HL/NHLBI NIH HHS; P01 HL116264/HL/NHLBI NIH HHS; R01 DK096859/DK/NIDDK NIH HHS; RC2 HL101681/HL/NHLBI NIH HHS; RC2-HL101681/HL/NHLBI NIH HHS; T32 HL007852/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, CD3; 0/CD3 antigen, zeta chain; 63231-63-0/RNA

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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