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Th1 inflammatory response with altered expression of profibrotic and vasoactive mediators in AT1A and AT1B double-knockout mice.

Publication ,  Journal Article
Ouyang, X; Le, TH; Roncal, C; Gersch, C; Herrera-Acosta, J; Rodriguez-Iturbe, B; Coffman, TM; Johnson, RJ; Mu, W
Published in: Am J Physiol Renal Physiol
October 2005

AT(1) double receptor (AT(1A) and AT(1B)) knockout mice have lower blood pressure, impaired growth, and develop early renal microvascular disease and tubulointerstitial injury. We hypothesized that there would be an increased expression of vasoactive, profibrotic, and inflammatory mediators expressed in the kidneys of AT(1) double-knockout mice. We examined the renal expression of various mediator systems in control (n = 6) vs. double-knockout mice (n = 6) at 3-5 mo of age by real-time PCR, immunohistochemistry, and Western blot analysis. AT(1) double-knockout mice show activation of Th1-dependent pathways (with increased expression of IFN-alpha, IL-2 mRNA) with increased expression of both monocyte (MCP-1 mRNA) and T cell (RANTES mRNA) chemokines, infiltration of CD4(+) and CD11b(+) cells, increased fibrosis-associated mediators (CTGF, TGF-beta and TNF-alpha mRNA) and extracellular matrix (collagens I and III mRNA and protein) deposition compared with controls (P < 0.05 for all markers). These changes were associated with increased mRNA expression of endothelin (ET)-1 and ET-A receptor (P < 0.05), cyclooxygenase (COX)-2/TXA2 synthase (P < 0.05), NADPH oxidase (p40-phox, p67-phox, P < 0.05) and iNOS and nNOS (P < 0.05). COX-2 and nNOS protein were also increased in the kidneys of AT(1) double-knockout mice by Western blot analysis (P < 0.05). Although renin and angiotensinogen mRNA expression were increased in the knockout mice, AT(2) receptor mRNA expression was not significantly different from wild-type mice. In conclusion, the absence of the AT(1) receptor is associated with marked renal alterations in vasoactive, profibrotic, and immune mediators with an inflammatory pattern favoring a Th1 phenotype.

Duke Scholars

Published In

Am J Physiol Renal Physiol

DOI

ISSN

1931-857X

Publication Date

October 2005

Volume

289

Issue

4

Start / End Page

F902 / F910

Location

United States

Related Subject Headings

  • Urology & Nephrology
  • Th1 Cells
  • Reverse Transcriptase Polymerase Chain Reaction
  • RNA
  • Oxidative Stress
  • NADPH Oxidases
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Macrophages
 

Citation

APA
Chicago
ICMJE
MLA
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Ouyang, X., Le, T. H., Roncal, C., Gersch, C., Herrera-Acosta, J., Rodriguez-Iturbe, B., … Mu, W. (2005). Th1 inflammatory response with altered expression of profibrotic and vasoactive mediators in AT1A and AT1B double-knockout mice. Am J Physiol Renal Physiol, 289(4), F902–F910. https://doi.org/10.1152/ajprenal.00141.2005
Ouyang, Xiaosen, Thu H. Le, Carlos Roncal, Christine Gersch, Jaime Herrera-Acosta, Bernardo Rodriguez-Iturbe, Thomas M. Coffman, Richard J. Johnson, and Wei Mu. “Th1 inflammatory response with altered expression of profibrotic and vasoactive mediators in AT1A and AT1B double-knockout mice.Am J Physiol Renal Physiol 289, no. 4 (October 2005): F902–10. https://doi.org/10.1152/ajprenal.00141.2005.
Ouyang X, Le TH, Roncal C, Gersch C, Herrera-Acosta J, Rodriguez-Iturbe B, et al. Th1 inflammatory response with altered expression of profibrotic and vasoactive mediators in AT1A and AT1B double-knockout mice. Am J Physiol Renal Physiol. 2005 Oct;289(4):F902–10.
Ouyang, Xiaosen, et al. “Th1 inflammatory response with altered expression of profibrotic and vasoactive mediators in AT1A and AT1B double-knockout mice.Am J Physiol Renal Physiol, vol. 289, no. 4, Oct. 2005, pp. F902–10. Pubmed, doi:10.1152/ajprenal.00141.2005.
Ouyang X, Le TH, Roncal C, Gersch C, Herrera-Acosta J, Rodriguez-Iturbe B, Coffman TM, Johnson RJ, Mu W. Th1 inflammatory response with altered expression of profibrotic and vasoactive mediators in AT1A and AT1B double-knockout mice. Am J Physiol Renal Physiol. 2005 Oct;289(4):F902–F910.

Published In

Am J Physiol Renal Physiol

DOI

ISSN

1931-857X

Publication Date

October 2005

Volume

289

Issue

4

Start / End Page

F902 / F910

Location

United States

Related Subject Headings

  • Urology & Nephrology
  • Th1 Cells
  • Reverse Transcriptase Polymerase Chain Reaction
  • RNA
  • Oxidative Stress
  • NADPH Oxidases
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Macrophages