プロフィール：准教授　松原 勤

准教授　松原 勤

　

准教授　松原 勤

Associate Professor: MATSUBARA, Tsutomu

matsu335(at)omu.ac.jp

自己紹介

遺伝子欠損マウスを用いたモデル動物の解析やオミクス解析を通して、非アルコール性脂肪肝炎などの肝疾患の分子病態を理解しようとしています。また、肝硬変治療薬の創薬研究や理学部や工学部の先生と協力して異分野融合型の基礎研究も行っています。

趣味として、野菜の自家栽培をやっています。

 

略歴

大阪府出身

2002年3月 東北大学薬学部薬学科　卒業
2007年3月 東北大学大学院薬学研究科 修了　博士(薬学)
2007年4月 東北大学大学院薬学研究科　博士研究員
2007年5月 米国国立衛生研究所(NIH)/国立がん研究所(NCI) Visiting Fellow
（2010年1月-2011年12月　日本学術振興会海外特別研究員(NIH)）
2012年1月 大阪市立大学大学院医学研究科　助教
2014年4月 大阪市立大学大学院医学研究科　講師
2016年7月 大阪市立大学大学院医学研究科　准教授
2022年4月 現職

　

研究・教育受賞歴
2012年度 大阪市立大学医学部長賞　優秀賞　受賞
2016年度 大阪市立大学医学部　Teacher of the year受賞
2022年度 大阪公立大学医学部　Teacher of the year受賞

　

主な研究業績

和文

  1. 松原勤, 河田則文. 肝星細胞活性化におけるnon-coding RNAネットワーク. 実験医学 2020;38(12):2046-2052.
  2. 松原勤. 質量分析装置を用いた薬物動態研究の新たな展開　医学・薬学研究におけるメタボロミクスの可能性. (一社)日本薬物動態学会　Drug Metabolism and Pharmacokinetics 2011；26(6)17-20

 

英文

  1. New Era of Immune-Based Therapy in Intrahepatic Cholangiocarcinoma.
    Kawamura E, Matsubara T, Kawada N.
    Cancers. 2023 Aug 6;15(15):3993. doi: 10.3390/cancers15153993.

 

  1. Huu Hoang T, Sato-Matsubara M, Yuasa H, Matsubara T, Thuy LTT, Ikenaga H, Phuong DM, Hanh NV, Hieu VN, Hoang DV, Hai H, Okina Y, Enomoto M, Tamori A, Daikoku A, Urushima H, Ikeda K, Dat NQ, Yasui Y, Shinkawa H, Kubo S, Yamagishi R, Ohtani N, Yoshizato K, Gracia-Sancho J, Kawada N. Cancer cells produce liver metastasis via gap formation in sinusoidal endothelial cells through proinflammatory paracrine mechanisms. Sci Adv. 2022 Sep 30;8(39):eabo5525. doi: 10.1126/sciadv.abo5525.

 

  1. Kawamura E, Matsubara T (#), Daikoku A, Deguchi S, Kinoshita M, Yuasa H, Urushima H, Odagiri N, Motoyama H, Kotani K, Kozuka R, Hagihara A, Fujii H, Uchida-Kobayashi S, Tanaka S, Takemura S, Iwaisako K, Enomoto M, Taguchi YH, Tamori A, Kubo S, Ikeda K, Kawada N. Suppression of intrahepatic cholangiocarcinoma cell growth by SKI via upregulation of the CDK inhibitor p21. FEBS Open Bio. 2022 Dec;12(12):2122-2135. doi: 10.1002/2211-5463.13489.

 

  1. Okina Y, Sato-Matsubara M, Kido Y, Urushima H, Daikoku A, Kadono C, Nakagama Y, Nitahara Y, Hoang TH, Thuy LTT, Matsubara T, Ohtani N, Ikeda K, Yoshizato K, Kawada N. Nitric oxide derived from cytoglobin-deficient hepatic stellate cells causes suppression of cytochrome c oxidase activity in hepatocytes. Antioxid Redox Signal. 2022 Sep 16. doi: 10.1089/ars.2021.0279.

 

  1. Yoshizato K, Taira T, Sato-Matsubara M, Sekiguchi S, Yabunaka Y, Kira Y, Ohashi T, Daikoku A, Ofusa K, Kadono C, Oikawa D, Matsubara T, Nakagama Y, Kido Y, Tokunaga F, Ikeda K, Kaneko A, Kawada N. Cloaking the ACE2 receptor with salivary cationic proteins inhibits SARS-CoV-2 entry.. J Biochem. 2022 Sep 30;172(4):205-216. doi: 10.1093/jb/mvac054.

 

  1. Oshimi K, Nishimura Y, Matsubara T, Tanaka M, Shikoh E, Zhao L, Zou Y, Komatsu N, Ikado Y, Takezawa Y, Kage-Nakadai E, Izutsu Y, Yoshizato K, Morita S, Tokunaga M, Yukawa H, Baba Y, Teki Y, Fujiwara M. Glass-patternable notch-shaped microwave architecture for on-chip spin detection in biological samples. Lab Chip. 2022 Jun 28;22(13):2519-2530. doi: 10.1039/d2lc00112h.

 

  1. Nishimura Y, Oshimi K, Umehara Y, Kumon Y, Miyaji K, Yukawa H, Shikano Y, Matsubara T, Fujiwara M, Baba Y, Teki Y. Wide-field fluorescent nanodiamond spin measurements toward real-time large-area intracellular thermometry. Sci Rep. 2021 Feb 19;11(1):4248. doi: 10.1038/s41598-021-83285-y.

 

  1. Kim JH, Matsubara T, Lee J, Fenollar-Ferrer C, Han K, Kim D, Jia S, Chang CJ, Yang H, Nagano T, Krausz KW, Yim SH, Gonzalez FJ. Lysosomal SLC46A3 modulates hepatic cytosolic copper homeostasis. Nat Commun. 2021 Jan 12;12(1):290. doi: 10.1038/s41467-020-20461-0.

 

  1. Urushima H, Yuasa H, Matsubara T, Kuroda N, Hara Y, Inoue K, Wake K, Sato T, Friedman SL, Ikeda K. Activation of Hepatic Stellate Cells Requires Dissociation of E-Cadherin-Containing Adherens Junctions with Hepatocytes. Am J Pathol. 2021 Mar;191(3):438-453. doi: 10.1016/j.ajpath.2020.12.007.

 

  1. Takada S, Matsubara T (*), Fujii H, Sato-Matsubara M, Daikoku A, Odagiri N, Amano-Teranishi Y, Kawada N, Ikeda K. Stress can attenuate hepatic lipid accumulation via elevation of hepatic β-muricholic acid levels in mice with nonalcoholic steatohepatitis. Lab Invest. 2021 Feb;101(2):193-203. doi: 10.1038/s41374-020-00509-x.

 

  1. Odagiri N, Matsubara T (#), Sato-Matsubara M, Fujii H, Enomoto M, Kawada N. Anti-fibrotic treatments for chronic liver diseases: The present and the future. Clin Mol Hepatol. 2021 Jul;27(3):413-424. doi: 10.3350/cmh.2020.0187.

 

  1. Okina Y, Sato-Matsubara M, Matsubara T, Daikoku A, Longato L, Rombouts K, Thanh Thuy LT, Ichikawa H, Minamiyama Y, Kadota M, Fujii H, Enomoto M, Ikeda K, Yoshizato K, Pinzani M, Kawada N. TGF-β1-driven reduction of cytoglobin leads to oxidative DNA damage in stellate cells during non-alcoholic steatohepatitis. J Hepatol. 2020 Oct;73(4):882-895. doi: 10.1016/j.jhep.2020.03.051.

 

  1. Konstandi M, Kypreos KE, Matsubara T, Xepapadaki E, Shah YM, Krausz K, Andriopoulou CE, Kofinas A, Gonzalez FJ. Adrenoceptor-related decrease in serum triglycerides is independent of PPARα activation. FEBS J. 2019 Nov;286(21):4328-4341. doi: 10.1111/febs.14966.

 

  1. Konstandi M, Sotiropoulos I, Matsubara T, Malliou F, Katsogridaki A, Andriopoulou CE, Gonzalez FJ. Adrenoceptor-stimulated inflammatory response in stress-induced serum amyloid A synthesis. Psychopharmacology (Berl). 2019 Jun;236(6):1687-1699. doi: 10.1007/s00213-018-5149-4.

 

  1. Odagiri N, Matsubara T (*), Higuchi M, Takada S, Urushima H, Sato-Matsubara M, Teranishi Y, Yoshizato K, Kawada N, Ikeda K. Involvement of ERK1/2 activation in the gene expression of senescence-associated secretory factors in human hepatic stellate cells. Mol Cell Biochem. 2019 May;455(1-2):7-19. doi: 10.1007/s11010-018-3466-x.

 

  1. Sato-Matsubara M, Matsubara T, Daikoku A, Okina Y, Longato L, Rombouts K, Thuy LTT, Adachi J, Tomonaga T, Ikeda K, Yoshizato K, Pinzani M, Kawada N. Fibroblast growth factor 2 (FGF2) regulates cytoglobin expression and activation of human hepatic stellate cells via JNK signaling. J Biol Chem. 2017 Nov 17;292(46):18961-18972. doi: 10.1074/jbc.M117.793794.

 

  1. Kim JH, Yamaori S, Tanabe T, Takagi M, Matsubara T, Okamoto M, Kimura S, Gonzalez FJ. Lack of epithelial PPARγ causes cystic adenomatoid malformations in mouse fetal lung. Biochem Biophys Res Commun. 2017 Sep 16;491(2):271-276. doi: 10.1016/j.bbrc.2017.07.113.

 

  1. Xu MJ, Cai Y, Wang H, Altamirano J, Chang B, Bertola A, Odena G, Lu J, Tanaka N, Matsusue K, Matsubara T, Mukhopadhyay P, Kimura S, Pacher P, Gonzalez FJ, Bataller R, Gao B. Fat-Specific Protein 27/CIDEC Promotes Development of Alcoholic Steatohepatitis in Mice and Humans. Gastroenterology. 2015 Oct;149(4):1030-41.e6. doi: 10.1053/j.gastro.2015.06.009.

 

  1. Manna SK, Golla S, Golla JP, Tanaka N, Cai Y, Takahashi S, Krausz KW, Matsubara T, Korboukh I, Gonzalez FJ. St. John's Wort Attenuates Colorectal Carcinogenesis in Mice through Suppression of Inflammatory Signaling. Cancer Prev Res (Phila). 2015 Sep;8(9):786-95. doi: 10.1158/1940-6207.CAPR-14-0113.

 

  1. Hayase S, Sasaki Y, Matsubara T, Seo D, Miyakoshi M, Murata T, Ozaki T, Kakudo K, Kumamoto K, Ylaya K, Cheng SY, Thorgeirsson SS, Hewitt SM, Ward JM, Kimura S. Expression of stanniocalcin 1 in thyroid side population cells and thyroid cancer cells. Thyroid. 2015 Apr;25(4):425-36. doi: 10.1089/thy.2014.0464.

 

  1. Teranishi Y, Matsubara T (#), Krausz KW, Le TT, Gonzalez FJ, Yoshizato K, Ikeda K, Kawada N. Involvement of hepatic stellate cell cytoglobin in acute hepatocyte damage through the regulation of CYP2E1-mediated xenobiotic metabolism. Lab Invest. 2015 May;95(5):515-24. doi: 10.1038/labinvest.2015.29.

 

  1. Sato M, Matsubara T, Adachi J, Hashimoto Y, Fukamizu K, Kishida M, Yang YA, Wakefield LM, Tomonaga T. Differential Proteome Analysis Identifies TGF-β-Related Pro-Metastatic Proteins in a 4T1 Murine Breast Cancer Model. PLoS One. 2015 May 18;10(5):e0126483. doi: 10.1371/journal.pone.0126483. eCollection 2015.

 

  1. Tanaka N, Takahashi S, Matsubara T, Jiang C, Sakamoto W, Chanturiya T, Teng R, Gavrilova O, Gonzalez FJ. Adipocyte-specific disruption of fat-specific protein 27 causes hepatosteatosis and insulin resistance in high-fat diet-fed mice. J Biol Chem. 2015 Jan 30;290(5):3092-105. doi: 10.1074/jbc.M114.605980.

 

  1. Tanaka N, Takahashi S, Fang ZZ, Matsubara T, Krausz KW, Qu A, Gonzalez FJ. Role of white adipose lipolysis in the development of NASH induced by methionine- and choline-deficient diet. Biochim Biophys Acta. 2014 Nov;1841(11):1596-607. doi: 10.1016/j.bbalip.2014.08.015.

 

  1. Manna SK, Tanaka N, Krausz KW, Haznadar M, Xue X, Matsubara T, Bowman ED, Fearon ER, Harris CC, Shah YM, Gonzalez FJ. Biomarkers of coordinate metabolic reprogramming in colorectal tumors in mice and humans. Gastroenterology. 2014 May;146(5):1313-24. doi: 10.1053/j.gastro.2014.01.017.

 

  1. Kido T, Yoneda M, Cai Y, Matsubara T, Ward JM, Kimura S. Secretoglobin superfamily protein SCGB3A2 deficiency potentiates ovalbumin-induced allergic pulmonary inflammation. Mediators Inflamm. 2014;2014:216465. doi: 10.1155/2014/216465.

 

  1. Kondo Y, Iwao T, Nakamura K, Sasaki T, Takahashi S, Kamada N, Matsubara T, Gonzalez FJ, Akutsu H, Miyagawa Y, Okita H, Kiyokawa N, Toyoda M, Umezawa A, Nagata K, Matsunaga T, Ohmori S. An efficient method for differentiation of human induced pluripotent stem cells into hepatocyte-like cells retaining drug metabolizing activity. Drug Metab Pharmacokinet. 2014;29(3):237-43. doi: 10.2133/dmpk.dmpk-13-rg-104.

 

  1. Ito S, Satoh J, Matsubara T, Shah YM, Ahn SH, Anderson CR, Shan W, Peters JM, Gonzalez FJ. Cholestasis induces reversible accumulation of periplakin in mouse liver. BMC Gastroenterol. 2013 Jul 13;13:116. doi: 10.1186/1471-230X-13-116.

 

  1. Li F, Lu J, Cheng J, Wang L, Matsubara T, Csanaky IL, Klaassen CD, Gonzalez FJ, Ma X. Human PXR modulates hepatotoxicity associated with rifampicin and isoniazid co-therapy. Nat Med. 2013 Apr;19(4):418-20. doi: 10.1038/nm.3104.

 

  1. Konstandi M, Shah YM, Matsubara T, Gonzalez FJ. Role of PPARα and HNF4α in stress-mediated alterations in lipid homeostasis. PLoS One. 2013 Aug 14;8(8):e70675. doi: 10.1371/journal.pone.0070675. eCollection 2013.

 

  1. Matsubara T, Tanaka N, Krausz KW, Manna SK, Kang DW, Anderson ER, Luecke H, Patterson AD, Shah YM, Gonzalez FJ. Metabolomics identifies an inflammatory cascade involved in dioxin- and diet-induced steatohepatitis. Cell Metab. 2012 Nov 7;16(5):634-44. doi: 10.1016/j.cmet.2012.10.006.

 

  1. Matsubara T, Tanaka N, Sato M, Kang DW, Krausz KW, Flanders KC, Ikeda K, Luecke H, Wakefield LM, Gonzalez FJ. TGF-β-SMAD3 signaling mediates hepatic bile acid and phospholipid metabolism following lithocholic acid-induced liver injury. J Lipid Res. 2012 Dec;53(12):2698-707. doi: 10.1194/jlr.M031773.

 

  1. Patterson AD, Shah YM, Matsubara T, Krausz KW, Gonzalez FJ. Peroxisome proliferator-activated receptor alpha induction of uncoupling protein 2 protects against acetaminophen-induced liver toxicity. Hepatology. 2012 Jul;56(1):281-90. doi: 10.1002/hep.25645.

 

  1. Tanaka N, Matsubara T, Krausz KW, Patterson AD, Gonzalez FJ. Disruption of phospholipid and bile acid homeostasis in mice with nonalcoholic steatohepatitis. Hepatology. 2012 Jul;56(1):118-29. doi: 10.1002/hep.25630. Epub 2012 Jun 6.

 

  1. Matsubara T, Li F, Gonzalez FJ. FXR signaling in the enterohepatic system. Mol Cell Endocrinol. 2013 Apr 10;368(1-2):17-29. doi: 10.1016/j.mce.2012.05.004.

 

  1. Ozaki T, Matsubara T, Seo D, Okamoto M, Nagashima K, Sasaki Y, Hayase S, Murata T, Liao XH, Hanson J, Rodriguez-Canales J, Thorgeirsson SS, Kakudo K, Refetoff S, Kimura S. Thyroid regeneration: characterization of clear cells after partial thyroidectomy. Endocrinology. 2012 May;153(5):2514-25. doi: 10.1210/en.2011-1365.

 

  1. Pang XY, Cheng J, Kim JH, Matsubara T, Krausz KW, Gonzalez FJ. Expression and regulation of human fetal-specific CYP3A7 in mice. Endocrinology. 2012 Mar;153(3):1453-63. doi: 10.1210/en.2011-1020.

 

  1. Bonzo JA, Ferry CH, Matsubara T, Kim JH, Gonzalez FJ. Suppression of hepatocyte proliferation by hepatocyte nuclear factor 4α in adult mice. J Biol Chem. 2012 Mar 2;287(10):7345-56. doi: 10.1074/jbc.M111.334599.

 

  1. Matsunaga T, Maruyama M, Matsubara T, Nagata K, Yamazoe Y, Ohmori S. Mechanisms of CYP3A induction by glucocorticoids in human fetal liver cells. Drug Metab Pharmacokinet. 2012;27(6):653-7. doi: 10.2133/dmpk.dmpk-12-nt-018.

 

  1. Jiang C, Qu A, Matsubara T, Chanturiya T, Jou W, Gavrilova O, Shah YM, Gonzalez FJ. Disruption of hypoxia-inducible factor 1 in adipocytes improves insulin sensitivity and decreases adiposity in high-fat diet-fed mice. Diabetes. 2011 Oct;60(10):2484-95. doi: 10.2337/db11-0174.

 

  1. Qu A, Taylor M, Xue X, Matsubara T, Metzger D, Chambon P, Gonzalez FJ, Shah YM. Hypoxia-inducible transcription factor 2α promotes steatohepatitis through augmenting lipid accumulation, inflammation, and fibrosis. Hepatology. 2011 Aug;54(2):472-83. doi: 10.1002/hep.24400.

 

  1. Kurotani R, Okumura S, Matsubara T, Yokoyama U, Buckley JR, Tomita T, Kezuka K, Nagano T, Esposito D, Taylor TE, Gillette WK, Ishikawa Y, Abe H, Ward JM, Kimura S. Secretoglobin 3A2 suppresses bleomycin-induced pulmonary fibrosis by transforming growth factor beta signaling down-regulation. J Biol Chem. 2011 Jun 3;286(22):19682-92. doi: 10.1074/jbc.M111.239046.

 

  1. Matsubara T, Tanaka N, Patterson AD, Cho JY, Krausz KW, Gonzalez FJ. Lithocholic acid disrupts phospholipid and sphingolipid homeostasis leading to cholestasis in mice. Hepatology. 2011 Apr;53(4):1282-93. doi: 10.1002/hep.24193.

 

  1. Taylor M, Qu A, Anderson ER, Matsubara T, Martin A, Gonzalez FJ, Shah YM. Hypoxia-inducible factor-2α mediates the adaptive increase of intestinal ferroportin during iron deficiency in mice. Gastroenterology. 2011 Jun;140(7):2044-55. doi: 10.1053/j.gastro.2011.03.007.

 

  1. Qu A, Shah YM, Matsubara T, Yang Q, Gonzalez FJ. PPARalpha-dependent activation of cell cycle control and DNA repair genes in hepatic nonparenchymal cells. Toxicol Sci. 2010 Dec;118(2):404-10. doi: 10.1093/toxsci/kfq259.

 

  1. Lee JH, Wada T, Febbraio M, He J, Matsubara T, Lee MJ, Gonzalez FJ, Xie W. A novel role for the dioxin receptor in fatty acid metabolism and hepatic steatosis. Gastroenterology. 2010 Aug;139(2):653-63. doi: 10.1053/j.gastro.2010.03.033.

 

  1. Wang T, Shah YM, Matsubara T, Zhen Y, Tanabe T, Nagano T, Fotso S, Krausz KW, Zabriskie TM, Idle JR, Gonzalez FJ. Control of steroid 21-oic acid synthesis by peroxisome proliferator-activated receptor alpha and role of the hypothalamic-pituitary-adrenal axis. J Biol Chem. 2010 Mar 5;285(10):7670-85. doi: 10.1074/jbc.M109.090175.

 

  1. Cho JY, Matsubara T, Kang DW, Ahn SH, Krausz KW, Idle JR, Luecke H, Gonzalez FJ. Urinary metabolomics in Fxr-null mice reveals activated adaptive metabolic pathways upon bile acid challenge. J Lipid Res. 2010 May;51(5):1063-74. doi: 10.1194/jlr.M002923.

 

  1. Shah YM, Matsubara T, Ito S, Yim SH, Gonzalez FJ. Intestinal hypoxia-inducible transcription factors are essential for iron absorption following iron deficiency. Cell Metab. 2009 Feb;9(2):152-64. doi: 10.1016/j.cmet.2008.12.012.

 

  1. Toriyabe T, Nagata K, Takada T, Aratsu Y, Matsubara T, Yoshinari K, Yamazoe Y. Unveiling a new essential cis element for the transactivation of the CYP3A4 gene by xenobiotics. Mol Pharmacol. 2009 Mar;75(3):677-84. doi: 10.1124/mol.108.050575.

 

  1. Matsubara T, Yoshinari K, Aoyama K, Sugawara M, Sekiya Y, Nagata K, Yamazoe Y. Role of vitamin D receptor in the lithocholic acid-mediated CYP3A induction in vitro and in vivo. Drug Metab Dispos. 2008 Oct;36(10):2058-63. doi: 10.1124/dmd.108.021501.

 

  1. Kamiyama Y, Matsubara T, Yoshinari K, Nagata K, Kamimura H, Yamazoe Y. Role of human hepatocyte nuclear factor 4alpha in the expression of drug-metabolizing enzymes and transporters in human hepatocytes assessed by use of small interfering RNA. Drug Metab Pharmacokinet. 2007 Aug;22(4):287-98. doi: 10.2133/dmpk.22.287.

 

  1. Kojima K, Nagata K, Matsubara T, Yamazoe Y. Broad but distinct role of pregnane x receptor on the expression of individual cytochrome p450s in human hepatocytes. Drug Metab Pharmacokinet. 2007 Aug;22(4):276-86. doi: 10.2133/dmpk.22.276.

 

  1. Matsubara T, Noracharttiyapot W, Toriyabe T, Yoshinari K, Nagata K, Yamazoe Y. Assessment of human pregnane X receptor involvement in pesticide-mediated activation of CYP3A4 gene. Drug Metab Dispos. 2007 May;35(5):728-33. doi: 10.1124/dmd.106.013144.

 

  1. Noracharttiyapot W, Nagai Y, Matsubara T, Miyata M, Shimada M, Nagata K, Yamazoe Y. Construction of several human-derived stable cell lines displaying distinct profiles of CYP3A4 induction. Drug Metab Pharmacokinet. 2006 Apr;21(2):99-108. doi: 10.2133/dmpk.21.99.

 

  1. Matsubara T, Kim HJ, Miyata M, Shimada M, Nagata K and Yamazoe Y. Isolation and characterization of a new major intestinal CYP3A form, CYP3A62, in the rat. J Pharmacol Exp Ther 2004;309:1282-1290.

 

  1. Matsumoto S, Hirama T, Matsubara T, Nagata K, Yamazoe Y. Involvement of CYP2J2 on the intestinal first-pass metabolism of antihistamine drug, astemizole. Drug Metab Dispos. 2002 Nov;30(11):1240-5. doi: 10.1124/dmd.30.11.1240.