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Kamada Y, Tamura S, Kiso S, et al. Angiotensin II stimulates the nuclear translocation of Smad2 and induces PAI-1 mRNA in rat hepatic stellate cells. Hepatol Res. 2003;25(3):296-305doi: 10.1016/s1386-6346(02)00306-6.
Kamada, Y., Tamura, S., Kiso, S., Fukui, K., Doi, Y., Ito, N., Terui, Y., Saito, T., Watanabe, H., Togashi, H., Kawata, S., & Matsuzawa, Y. (2003). Angiotensin II stimulates the nuclear translocation of Smad2 and induces PAI-1 mRNA in rat hepatic stellate cells. Hepatology research : the official journal of the Japan Society of Hepatology, 25(3), 296-305. https://doi.org/10.1016/s1386-6346(02)00306-6
Kamada, Yoshihiro, et al. "Angiotensin II stimulates the nuclear translocation of Smad2 and induces PAI-1 mRNA in rat hepatic stellate cells." Hepatology research : the official journal of the Japan Society of Hepatology vol. 25,3 (2003): 296-305. doi: https://doi.org/10.1016/s1386-6346(02)00306-6
Kamada Y, Tamura S, Kiso S, Fukui K, Doi Y, Ito N, Terui Y, Saito T, Watanabe H, Togashi H, Kawata S, Matsuzawa Y. Angiotensin II stimulates the nuclear translocation of Smad2 and induces PAI-1 mRNA in rat hepatic stellate cells. Hepatol Res. 2003 Mar;25(3):296-305. doi: 10.1016/s1386-6346(02)00306-6. PMID: 12697251.
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Hepatol Res. 2003 Mar;25(3):296-305. doi: 10.1016/s1386-6346(02)00306-6.

Angiotensin II stimulates the nuclear translocation of Smad2 and induces PAI-1 mRNA in rat hepatic stellate cells.

Hepatology research : the official journal of the Japan Society of Hepatology

Yoshihiro Kamada, Shinji Tamura, Shinichi Kiso, Koji Fukui, Yoshinori Doi, Nobuyuki Ito, Yuki Terui, Takafumi Saito, Hisayoshi Watanabe, Hitoshi Togashi, Sumio Kawata, Yuji Matsuzawa

Affiliations

  1. Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, 2-2, B5, Yamada-oka, Suita, 565-0871, Osaka, Japan

PMID: 12697251 DOI: 10.1016/s1386-6346(02)00306-6

Abstract

It has recently been reported that angiotensin II (ANGII) stimulates gene expression of transforming growth factor-beta1 (TGF-beta1) and is involved in hepatic fibrosis. This effect is thought to be caused through ANGII type 1 receptor (ATR1). However, a role of ANGII at the postreceptor levels of TGF-beta1 signaling has not been identified. To clarify the role of ANGII on hepatic fibrosis, we investigated the effect of ANGII on rat hepatic stellate cells (HSCs). HSCs were isolated from male Sprague-Dawley rats. TGF-beta1 and matrix protein gene expression in HSCs was assessed by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) using SYBR Green I. The nuclear translocation of Smad2 in HSCs after 20 min ANGII stimulation was analyzed by Western blotting. ANGII was found to induce TGF-beta1 and matrix protein gene expression in HSCs. The nuclear translocation of Smad2 in HSCs was also induced by ANGII stimulation. These effects of ANGII were almost completely blocked by the ATR1 antagonist, CS-866. ANGII induces TGF-beta1 and matrix protein mRNA, and stimulates rapid nuclear translocation of Smad2 in rat HSCs through ATR1, which indicates that the ATR1 blockade represents a novel approach for the possible prevention of hepatic fibrosis.

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