私の胆汁酸研究の歩み

加川 建弘

東海大学医学部消化器内科

 1993年に慶應義塾大学から東海大学に移り、胆汁酸の研究を開始しました。胆汁分泌機構に興味があり、主に胆汁酸トランスポーターの調節機構、遺伝子異常による機能異常、細胞内移送機構について研究を行ってきました。1999年10月から2002年3月まではタフツ大学生理学のIrwin M. Arias教授研究室に留学、2002年4月からは東海大学にもどり、胆汁分泌機構に関する研究を続けています。

 なお、東海大学での共同研究者である渡辺勲史先生は、慶應義塾大学消化器内科からトロント大学M. J. Phillips教授のところに留学され、胆汁分泌における毛細胆管収縮の果たす役割について研究をされていました。

 強調したい論文を橙色で示します。

• Kagawa T, Watanabe N, Sato M, et al. Differential expression of multidrug resistance (mdr) and canalicular multispecific organic anion transporter (cMOAT) genes following extrahepatic biliary obstruction in rats. Biochem. Mol. Biol. Int. 4: 443-452, 1998.
• Kagawa T, Sato M, Hosoi K, et al. Absence of R1066X mutation in six Japanese patients with Dubin-Johnson syndrome. Biochem. Mol. Biol. Int. 47: 639-644, 1999.
• Kagawa T, Varticovski L, Sai Y, et al. Mechanism by which cAMP activates PI3-kinase and increases bile acid secretion in WIF-B9 cells. Am. J. Physiol. Cell Physiol. 283: C1655-1666, 2002.
• Harris MJ, Kagawa T, Dawson PA, et al. Taurocholate transport by hepatic and intestinal bile acid transporters is independent of FIC1 overexpression in Madin-Darby canine kidney cells. J. Gastroenterol. Hepatol. 19: 819-825, 2004.
• Watanabe N, Takasimizu S, Kojima S, et al. Altered cell motility behaviour and reorganization of contractile proteins after primary monolayer cultures ofisolated hepatocytes. The Tokai Journal of Experimental and Clinical Medicine 32: 34-41, 2007.
• Watanabe N, Takasimizu S, Kojima S, et al. Clinical and pathological features of a prolonged type of acute intrahepatic cholestasis. Hepatol. Res. 37: 598-607, 2007.
• Watanabe N, Kojima S, Takashimizu S, et al. Initial site of bile regurgitation following extrahepatic biliary obstruction in living rats. J. Gastroenterol. Hepatol. 22: 1983-1992, 2007.
• Watanabe N, Kagawa T, Kojima S, et al. Taurolithocholate impairs bile canalicular motility and canalicular bile secretion in isolated rat hepatocyte couplets. World J. Gastroenterol. 12: 5320-5325, 2006.
• Watanabe N, Takashimizu S, Shiraishi K, et al. Primary biliary cirrhosis with multinucleated hepatocellular giant cells: implications for pathogenesis of primary biliary cirrhosis. Eur. J. Gastroenterol. Hepatol. 18: 1023-1027, 2006.
• Watanabe N, Takashimizu S, Nishizaki Y, et al. An ETA receptor antagonist induces the dilatation of sinusoidal endothelial fenestrae: Implication for endothelin-1 in hepatic microcirculation. J. Gastroenterol. 42: 775-782, 2007.
• Mochizuki K, Kagawa T, Numari A, et al. Two N-linked glycans are required to maintain the transport activity of the bile salt export pump (ABCB11) in MDCK II cells. Am. J. Physiol. Gastrointest. Liver Physiol. 292: G818-828, 2007.
• Kagawa T, Watanabe N, Mochizuki K, et al. Phenotypic differences in PFIC2 and BRIC2 correlate with protein stability of mutant Bsep and impaired taurocholate secretion in MDCK II cells. Am. J. Physiol. Gastrointest. Liver Physiol. 294: G58-67, 2008.
• Miyata M, Hata T, Yamakawa H, et al. Involvement of multiple elements in FXR-mediated transcriptional activation of FGF19. J. Steroid Biochem. Mol. Biol. 132: 41-47, 2012.
• Kagawa T, Orii R, Hirose S, Arase Y, et al. Ursodeoxycholic acid stabilizes the bile salt export pump in the apical membrane in MDCK II cells. J. Gastroenterol. 49: 890-899, 2014.
• Kagawa T, Hirose S, Arase Y, et al. No contribution of the ABCB11 p.444A polymorphism in Japanese patients with drug-induced cholestasis. Drug Metab. Dispos. 43: 691-697, 2015.
• Kagawa T, Oka A, Kobayashi Y, et al. Recessive inheritance of population-specific intronic LINE-1 insertion causes a Rotor syndrome phenotype. Hum. Mutat. 36: 327-332, 2015.
• Kagawa T, Adachi Y, Hashimoto N, et al. Loss of organic anion transporting polypeptide 1B3 function causes marked delay in indocyanine green clearance without any clinical symptoms. Hepatology. 65: 1065-1068, 2017.

 渡辺勲史論文

• Watanabe N, Tsukada N, Smith CR, et al. Permeabilized hepatocyte couplets. Adenosine triphosphate-dependent bile canalicular contractions and a circumferential pericanalicular microfilament belt demonstrated. Lab. Invest. 65: 203-13, 1991.
• Watanabe N, Tsukada N, Smith CR, et al. Motility of bile canaliculi in the living animal: implications for bile flow. J. Cell Biol. 113: 1069-1080, 1991.