Angiotensin II Regulates Liver Regeneration via Type 1 Receptor Following Partial Hepatectomy in Mice(Pharmacology)
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概要
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Angiotensin II (Ang II) is an important mediator stimulating liver fibrosis after liver injury. However, it is not known whether Ang II plays a role in liver regeneration. Here, we investigate the effects of Ang II type 1 (AT_1) receptor blocker (ARB), angiotensin-converting enzyme inhibitor (ACEI), systemic infusion of Ang II, and genetic deficiency of the AT_<1a> receptor (AT1a-KO) on the hepatic regenerative response to partial hepatectomy (PH) in mice. Administration of ARE (candesartan cilexetil and losartan) or ACEI (enarapril and lisinopril) enhanced 5-bromo-2'-deoxyuridine (BrdU) incorporation into hepatocyte nuclei in remnant liver as well as the restoration of liver weight after PH. Systemic infusion of Ang II (100 ng/kg/min) suppressed the PH-induced BrdU incorporation and the restoration of liver weight. In contrast to Ang II infusion, these hepatic responses to PH were significantly greater in AT1a-KO mice than in wild-type mice. The PH-induced increases in hepatic levels of hepatocyte growth factor (HGF) mRNA and plasma HGF concentrations were greater in candesartan- and enarapril-treated mice or in AT1a-KO mice than in vehicle-treated mice or wild-type mice, respectively, whereas they were less in Ang II-infused mice than in vehicle-infused mice. In contrast to HGF, blockades of the renin-angiotensin system or Ang II infusion produced opposite effects on the PH-induce increases in hepatic transforming growth factor (TGF)-beta 1 mRNA and plasma TGF-beta 1 levels. These studies suggest that Ang II plays a role in the liver regeneration as a suppressor of hepatocyte proliferation via the AT_1 receptor-mediated control of growth factor production.
- 公益社団法人日本薬学会の論文
- 2008-07-01
著者
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FUKAMIZU Akiyoshi
Center for Tsukuba Advanced Research Alliance, Graduate School of Life and Environmental Sciences, U
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屋山 勝俊
神戸学院大学薬学部 生命薬学部門 循環器薬理学研究室
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Sugaya Takeshi
Center For Tsukuba Advanced Research Alliance University Of Tsukuba
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YAYAMA Katsutoshi
Laboratory of Cardiovascular Pharmacology, Department of Biopharmaceutical Sciences, Kobe Gakuin Uni
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MIYAGI Ryoko
Laboratory of Cardiovascular Pharmacology, Department of Biopharmaceutical Sciences, Kobe Gakuin Uni
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SUGIYAMA Kaori
Laboratory of Cardiovascular Pharmacology, Department of Biopharmaceutical Sciences, Kobe Gakuin Uni
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OKAMOTO Hiroshi
Laboratory of Cardiovascular Pharmacology, Department of Biopharmaceutical Sciences, Kobe Gakuin Uni
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Fukamizu Akiyoshi
Center For Tsukuba Advanced Research Alliance University Of Tsukuba
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Fukamizu Akiyoshi
Center For Tsukuba Advanced Research Alliance And Institute Of Applied Biochemistry University Of Ts
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Okamaoto H
Laboratory Of Cardiovascular Pharmacology Department Of Biopharmaceutical Sciences Kobe Gakuin Unive
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Okamoto H
Department Of Systems And Control Engineering Anan National College Of Technology
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Sugiyama Kaori
Laboratory Of Cardiovascular Pharmacology Department Of Biopharmaceutical Sciences Kobe Gakuin Unive
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岡本 宏巳
Department Of Pharmacology Faculty Of Pharmaceutical Sciences Kobe Gakuin University
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屋山 勝俊
Laboratory Of Cardiovascular Pharmacology Department Of Biopharmaceutical Sciences Kobe Gakuin Unive
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Miyagi Ryoko
Laboratory Of Cardiovascular Pharmacology Department Of Biopharmaceutical Sciences Kobe Gakuin Unive
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Yayama Katsutoshi
Laboratory Of Cardiovascular Pharmacology Department Of Biopharmaceutical Sciences Kobe Gakuin Unive
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Okamoto Hiroshi
Laboratory Of Cardiovascular Pharmacology Department Of Biopharmaceutical Sciences Kobe Gakuin Unive
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