Skip to main content
Journal cover image

Attenuated hepatic inflammation and fibrosis in angiotensin type 1a receptor deficient mice.

Publication ,  Journal Article
Yang, L; Bataller, R; Dulyx, J; Coffman, TM; Ginès, P; Rippe, RA; Brenner, DA
Published in: J Hepatol
August 2005

BACKGROUND/AIMS: Pharmacological blockade of the renin-angiotensin system (RAS) attenuates liver fibrogenesis in rats. Here, we provide genetic evidence implicating angiotensin type 1 (AT1) receptors in liver fibrogenesis. METHODS: Wild type (WT) and AT1a knockout [AT1a (-/-)] mice were subjected to either sham operation or bile-duct ligation. Fibrosis was assessed by Sirius Red staining and hydroxyproline hepatic content. Fibrogenic and inflammatory cytokines were measured by ELISA. RESULTS: Bile duct ligation-induced elevation of serum liver enzymes was similar in WT and AT1a (-/-) mice. Bile duct ligated WT mice showed inflammatory changes and severe septal fibrosis. In contrast, AT1a (-/-) mice showed minor fibrotic lesions. Collagen accumulation was lower in AT1a (-/-) mice compared to WT mice. The increase in hepatic concentration of TGFbeta1 and pro-inflammatory cytokines was attenuated in AT1a (-/-) mice compared to WT mice. Immunohistochemistry analysis revealed decreased infiltration by inflammatory cells, lipid peroxidation products as well as decreased phosphorylation of c-Jun and p42/44 MAPK in AT1a (-/-) mice compared to AT1 (+/+) mice. CONCLUSIONS: AT1 receptors play an important role in the development of fibrosis. Pharmacological blockade of AT1 receptors appears to be a promising approach to treat liver fibrosis.

Duke Scholars

Published In

J Hepatol

DOI

ISSN

0168-8278

Publication Date

August 2005

Volume

43

Issue

2

Start / End Page

317 / 323

Location

Netherlands

Related Subject Headings

  • Transforming Growth Factor beta1
  • Transforming Growth Factor beta
  • Reverse Transcriptase Polymerase Chain Reaction
  • Receptor, Angiotensin, Type 1
  • RNA
  • Phosphorylation
  • Mitogen-Activated Protein Kinase 1
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Yang, L., Bataller, R., Dulyx, J., Coffman, T. M., Ginès, P., Rippe, R. A., & Brenner, D. A. (2005). Attenuated hepatic inflammation and fibrosis in angiotensin type 1a receptor deficient mice. J Hepatol, 43(2), 317–323. https://doi.org/10.1016/j.jhep.2005.02.034
Yang, Liu, Ramón Bataller, Jennyfer Dulyx, Thomas M. Coffman, Pere Ginès, Richard A. Rippe, and David A. Brenner. “Attenuated hepatic inflammation and fibrosis in angiotensin type 1a receptor deficient mice.J Hepatol 43, no. 2 (August 2005): 317–23. https://doi.org/10.1016/j.jhep.2005.02.034.
Yang L, Bataller R, Dulyx J, Coffman TM, Ginès P, Rippe RA, et al. Attenuated hepatic inflammation and fibrosis in angiotensin type 1a receptor deficient mice. J Hepatol. 2005 Aug;43(2):317–23.
Yang, Liu, et al. “Attenuated hepatic inflammation and fibrosis in angiotensin type 1a receptor deficient mice.J Hepatol, vol. 43, no. 2, Aug. 2005, pp. 317–23. Pubmed, doi:10.1016/j.jhep.2005.02.034.
Yang L, Bataller R, Dulyx J, Coffman TM, Ginès P, Rippe RA, Brenner DA. Attenuated hepatic inflammation and fibrosis in angiotensin type 1a receptor deficient mice. J Hepatol. 2005 Aug;43(2):317–323.
Journal cover image

Published In

J Hepatol

DOI

ISSN

0168-8278

Publication Date

August 2005

Volume

43

Issue

2

Start / End Page

317 / 323

Location

Netherlands

Related Subject Headings

  • Transforming Growth Factor beta1
  • Transforming Growth Factor beta
  • Reverse Transcriptase Polymerase Chain Reaction
  • Receptor, Angiotensin, Type 1
  • RNA
  • Phosphorylation
  • Mitogen-Activated Protein Kinase 1
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice