Biochemical and Biophysical Research Communications
AT1A-deficient mice show less severe progression of liver fibrosis induced by CCl4
Section snippets
Materials and methods
Animals. AT1A-deficient mice were established by Sugaya et al. [12], and a kind gift from Tanabe Seiyaku (Osaka, Japan) and C57BL/6 mice were obtained from Hiroshima Jikken Doubutsu (Hiroshima, Japan). Both strains of mice have the same genetic background and animals aged 6–8 weeks were used in the present study. The mice were allowed free access to food and water, and were housed at a constant temperature with a 12-h light/dark cycle during the study. To assess the necrotic and inflammatory
AT1 mRNA expression
To confirm the absence of AT1 receptors in AT1A-deficient mice, RT-PCR was performed to evaluate hepatic mRNA levels of AT1. The expression of AT1 mRNA was not observed in the liver of AT1A-deficient mice, whereas it was seen in that of WT mice (Fig. 1).
Parameters of necrosis/inflammation
To determine whether absence of the AT1A receptor had any influence on necrosis and inflammation caused by acute exposure to CCl4, serum transaminases and the proinflammatory cytokine TNF-α were measured. There were no significant differences of
Discussion
In the cardiovascular system and the kidneys, blockade of Ang II has been shown to prevent fibrosis and inflammatory cell infiltration [19], [20], [21], [22]. Ang II could also be involved in the process of fibrogenesis because of its action as a proinflammatory cytokine, participating in various steps of the inflammatory response. Interestingly, systemic infusion of Ang II results in significant cardiac and renal fibrosis, but no fibrotic response occurs in the liver [23].
Previous in vitro
Acknowledgements
The authors thank Dr. Takeshi Sugaya (Discovery Research Laboratory, Tanabe Seiyaku Co. Ltd., Osaka) for providing the Angiotensin II type 1A receptor-deficient mice. This study was partly supported by a grant from the Japanese Ministry of Education, Culture, Sports, Science and Technology to Dr. Tazuma (No. 12670489).
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