{"id":396,"date":"2026-02-19T00:46:22","date_gmt":"2026-02-18T15:46:22","guid":{"rendered":"https:\/\/www.med.osaka-u.ac.jp\/pub\/gh\/wp\/research\/research-detail\/research-group-1\/"},"modified":"2026-02-19T00:46:22","modified_gmt":"2026-02-18T15:46:22","slug":"research-group-1","status":"publish","type":"page","link":"https:\/\/www.med.osaka-u.ac.jp\/pub\/gh\/research\/research-detail\/research-group-1\/","title":{"rendered":"\u809d\u7d30\u80de\u6b7b\u30fb\u809d\u661f\u7d30\u80de\u5fae\u5c0f\u74b0\u5883\u7814\u7a76\u30b0\u30eb\u30fc\u30d7"},"content":{"rendered":"\n\n
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\u809d\u7d30\u80de\u6b7b\u30fb\u809d\u661f\u7d30\u80de\u5fae\u5c0f\u74b0\u5883\u7814\u7a76\u30b0\u30eb\u30fc\u30d7<\/h2>\n <\/div>\n\n
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\u30b0\u30eb\u30fc\u30d7\u30ea\u30fc\u30c0\u30fc\uff1a\u9f4b\u85e4\u7fa9\u4fee<\/h2>\n

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\u672c\u30b0\u30eb\u30fc\u30d7\u306f\u3001\u809d\u7d30\u80de\u6b7b\uff08\u30a2\u30dd\u30c8\u30fc\u30b7\u30b9\u304a\u3088\u3073\u975e\u30a2\u30dd\u30c8\u30fc\u30b7\u30b9\u578b\uff09\u3092\u8d77\u70b9\u306b\u3001\u708e\u75c7\u30fb\u514d\u75ab\u5fdc\u7b54\u3001\u809d\u661f\u7d30\u80de\u3092\u4e2d\u5fc3\u3068\u3059\u308b\u5fae\u5c0f\u74b0\u5883\u306e\u5909\u5bb9\u3001\u7dda\u7dad\u5316\u3001\u809d\u767a\u764c\u3078\u3068\u9023\u306a\u308b\u6162\u6027\u809d\u75be\u60a3\u306e\u75c5\u614b\u9023\u9396\u3092\u7d71\u5408\u7684\u306b\u89e3\u660e\u3057\u307e\u3059\u3002\u5358\u4e00\u7d30\u80deRNA\u89e3\u6790\uff08single-cell RNA-seq\uff09\u30fb\u7a7a\u9593\u7684\u30c8\u30e9\u30f3\u30b9\u30af\u30ea\u30d7\u30c8\u30fc\u30e0\uff08spatial transcriptomics\uff09\u30fb\u30af\u30ed\u30de\u30c1\u30f3\u89e3\u6790\u306b\u3001\u30de\u30a6\u30b9\u30e2\u30c7\u30eb\u3001\u30aa\u30eb\u30ac\u30ce\u30a4\u30c9\u3001\u5171\u57f9\u990a\u7cfb\u3092\u7d44\u307f\u5408\u308f\u305b\u3001\u809d\u661f\u7d30\u80de\u30b5\u30d6\u30dd\u30d4\u30e5\u30ec\u30fc\u30b7\u30e7\u30f3\u306e\u6a5f\u80fd\u3001\u7d30\u80de\u9593\u30b7\u30b0\u30ca\u30eb\u3001\u8ee2\u5199\u5236\u5fa1\u30cd\u30c3\u30c8\u30ef\u30fc\u30af\u3092\u660e\u3089\u304b\u306b\u3057\u307e\u3059\u3002\u3055\u3089\u306b\u81e8\u5e8a\u691c\u4f53\uff08\u751f\u691c\u30fb\u5207\u9664\u7d44\u7e54\u30fb\u8840\u6db2\uff09\u3067\u691c\u8a3c\u3057\u3001\u30d0\u30a4\u30aa\u30de\u30fc\u30ab\u30fc\u958b\u767a\u3068\u6cbb\u7642\u4ecb\u5165\u306e\u691c\u8a3c\u3092\u901a\u3058\u3066\u3001\u6a4b\u6e21\u3057\u7814\u7a76\uff08Translational Research\uff09\u306b\u3088\u308b\u65b0\u898f\u4e88\u9632\u85ac\u30fb\u6cbb\u7642\u85ac\u306e\u5275\u51fa\u3092\u76ee\u6307\u3057\u307e\u3059\u3002<\/p>\n <\/div>\n\n

\n \"\u7814\u7a76\u6982\u8981\u56f3\"\n <\/div>\n <\/div>\n\n
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\u809d\u7d30\u80de\u6b7b\u3092\u8d77\u70b9\u3068\u3059\u308b\u6162\u6027\u809d\u75be\u60a3\u306e\u75c5\u614b\u9032\u5c55\u6a5f\u5e8f\u306e\u89e3\u660e<\/h3>\n

\u809d\u7d30\u80de\u6b7b\u306e\u30bf\u30a4\u30d7\uff08\u30a2\u30dd\u30c8\u30fc\u30b7\u30b9\uff0f\u975e\u30a2\u30dd\u30c8\u30fc\u30b7\u30b9\u578b\u7d30\u80de\u6b7b\uff09\u304c\u6162\u6027\u809d\u75be\u60a3\u306e\u75c5\u614b\u3092\u3069\u306e\u3088\u3046\u306b\u898f\u5b9a\u3057\u3001\u7dda\u7dad\u5316\u30fb\u767a\u764c\u306e\u9032\u5c55\u306b\u5bc4\u4e0e\u3059\u308b\u304b\u3092\u89e3\u6790\u3057\u307e\u3059\u3002\u7d30\u80de\u6b7b\u306b\u4f34\u3046DAMPs\u653e\u51fa\u3092\u8d77\u70b9\u3068\u3057\u3066\u6d3b\u6027\u5316\u3055\u308c\u308b\u53d7\u5bb9\u4f53\u30b7\u30b0\u30ca\u30eb\u3001\u30b5\u30a4\u30c8\u30ab\u30a4\u30f3\uff0f\u30b1\u30e2\u30ab\u30a4\u30f3\u56de\u8def\u3001\u514d\u75ab\u7d30\u80de\uff08\u30de\u30af\u30ed\u30d5\u30a1\u30fc\u30b8\u3001\u597d\u4e2d\u7403\u3001T\u7d30\u80de\u7b49\uff09\u306e\u6642\u7a7a\u9593\u30c0\u30a4\u30ca\u30df\u30af\u30b9\u3092\u3001\u5f53\u30b0\u30eb\u30fc\u30d7\u304c\u69cb\u7bc9\u3057\u3066\u304d\u305f\u809d\u7d30\u80de\u6b7b\u8a98\u5c0e\u30e2\u30c7\u30eb\uff08in vivo\/in vitro\uff09\u3067\u7cfb\u7d71\u7684\u306b\u691c\u8a3c\u3057\u3001\u75c5\u614b\u9032\u5c55\u306e\u56e0\u679c\u6a5f\u5e8f\u3092\u660e\u3089\u304b\u306b\u3057\u307e\u3059\u3002\u3055\u3089\u306b\u5f97\u3089\u308c\u305f\u77e5\u898b\u3092\u81e8\u5e8a\u691c\u4f53\uff08\u751f\u691c\u30fb\u5207\u9664\u7d44\u7e54\u30fb\u8840\u6db2\uff09\u3067\u691c\u8a3c\u3057\u3001\u9032\u5c55\u4e88\u6e2c\u30d0\u30a4\u30aa\u30de\u30fc\u30ab\u30fc\u306e\u540c\u5b9a\u3068\u3001\u6cbb\u7642\u6a19\u7684\u5019\u88dc\u306e\u5275\u51fa\u3092\u76ee\u6307\u3059\u3002<\/p>\n <\/div>\n\n

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\n \"\u7814\u7a76\u5185\u5bb9\u56f3\"\n <\/div>\n\n
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\n \"\u7814\u7a76\u5185\u5bb9\u56f3\"\n <\/div>\n <\/section>\n\n
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\u5c06\u6765\u5c55\u671b\uff1a\u75c5\u614b\u9023\u9396\u306e\u53ef\u8996\u5316\u3068\u5c64\u5225\u5316\u306b\u57fa\u3065\u304f\u500b\u5225\u5316\u533b\u7642\u306e\u5b9f\u88c5<\/h3>\n

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\u3010\u4e3b\u8981\u8ad6\u6587\u3011<\/h3>\n
    \n
  1. Kudo S, Hikita H, Saito Y, Murai K, Kodama T, Tatsumi T, Takehara T. Collaborative orchestration of BH3-only proteins governs Bak\/Bax-dependent hepatocyte apoptosis under antiapoptotic protein-deficiency in mice. Cell Death Differ. 2025 Jun;32(6):1153-1166.<\/li>\n
  2. Sugimoto A, Saito Y, Wang G, Sun Q, Yin C, Lee KH, Geng Y, Rajbhandari P, Hernandez C, Steffani M, Qie J, Savage T, Goyal DM, Ray KC, Neelakantan TV, Yin D, Melms J, Lehrich BM, Yasaka TM, Liu S, Oertel M, Lan T, Guillot A, Peiseler M, Filliol A, Kanzaki H, Fujiwara N, Ravi S, Izar B, Brosch M, Hampe J, Remotti H, Argemi J, Sun Z, Kendall TJ, Hoshida Y, Tacke F, Fallowfield JA, Blockley-Powell SK, Haeusler RA, Steinman JB, Pajvani UB, Monga SP, Bataller R, Masoodi M, Arpaia N, Lee YA, Stockwell BR, Augustin HG, Schwabe RF. Hepatic stellate cells control liver zonation, size and functions via R-spondin 3. Nature. 2025 Apr;640(8059):752-761.<\/li>\n
  3. Saito Y, Yin D, Kubota N, Wang X, Filliol A, Remotti H, Nair A, Fazlollahi L, Hoshida Y, Tabas I, Wangensteen KJ, Schwabe RF. A Therapeutically Targetable TAZ-TEAD2 Pathway Drives the Growth of Hepatocellular Carcinoma via ANLN and KIF23. Gastroenterology. 2023 Jun;164(7):1279-1292.<\/li>\n
  4. Filliol A, Saito Y, Nair A, Dapito DH, Yu LX, Ravichandra A, Bhattacharjee S, Affo S, Fujiwara N, Su H, Sun Q, Savage TM, Wilson-Kanamori JR, Caviglia JM, Chin L, Chen D, Wang X, Caruso S, Kang JK, Amin AD, Wallace S, Dobie R, Yin D, Rodriguez-Fiallos OM, Yin C, Mehal A, Izar B, Friedman RA, Wells RG, Pajvani UB, Hoshida Y, Remotti HE, Arpaia N, Zucman-Rossi J, Karin M, Henderson NC, Tabas I, Schwabe RF. Opposing roles of hepatic stellate cell subpopulations in hepatocarcinogenesis. Nature. 2022 Oct;610(7931):356-365.<\/li>\n
  5. Wang X, Zeldin S, Shi H, Zhu C, Saito Y, Corey KE, Osganian SA, Remotti HE, Verna EC, Pajvani UB, Schwabe RF, Tabas I. TAZ-induced Cybb contributes to liver tumor formation in non-alcoholic steatohepatitis. J Hepatol. 2022 Apr;76(4):910-920.<\/li>\n
  6. Affo S, Nair A, Brundu F, Ravichandra A, Bhattacharjee S, Matsuda M, Chin L, Filliol A, Wen W, Song X, Decker A, Worley J, Caviglia JM, Yu L, Yin D, Saito Y, Savage T, Wells RG, Mack M, Zender L, Arpaia N, Remotti HE, Rabadan R, Sims P, Leblond AL, Weber A, Riener MO, Stockwell BR, Gaublomme J, Llovet JM, Kalluri R, Michalopoulos GK, Seki E, Sia D, Chen X, Califano A, Schwabe RF. Promotion of cholangiocarcinoma growth by diverse cancer-associated fibroblast subpopulations. Cancer Cell. 2021 Jun 14;39(6):866-882.e11.<\/li>\n
  7. Mizutani N, Hikita H, Saito Y, Myojin Y, Sato K, Urabe M, Kurahashi T, Shiode Y, Sakane S, Murai K, Nozaki Y, Kodama T, Sakamori R, Yoshida Y, Tatsumi T, Takehara T. Gab1 in livers with persistent hepatocyte apoptosis has an antiapoptotic effect and reduces chronic liver injury, fibrosis, and tumorigenesis. Am J Physiol Gastrointest Liver Physiol. 2021 Jun 1;320(6):G958-G968.<\/li>\n
  8. Nozaki Y, Hikita H, Tanaka S, Fukumoto K, Urabe M, Sato K, Myojin Y, Doi A, Murai K, Sakane S, Saito Y, Kodama T, Sakamori R, Tatsumi T, Takehara T. Persistent hepatocyte apoptosis promotes tumorigenesis from diethylnitrosamine-transformed hepatocytes through increased oxidative stress, independent of compensatory liver regeneration. Sci Rep. 2021 Feb 9;11(1):3363.<\/li>\n
  9. Saito Y, Hikita H, Nozaki Y, Kai Y, Makino Y, Nakabori T, Tanaka S, Yamada R, Shigekawa M, Kodama T, Sakamori R, Tatsumi T, Takehara T. DNase II activated by the mitochondrial apoptotic pathway regulates RIP1-dependent non-apoptotic hepatocyte death via the TLR9\/IFN-\u03b2 signaling pathway. Cell Death Differ. 2019 Mar;26(3):470-486.<\/li>\n
  10. Tanaka S, Hikita H, Tatsumi T, Sakamori R, Nozaki Y, Sakane S, Shiode Y, Nakabori T, Saito Y, Hiramatsu N, Tabata K, Kawabata T, Hamasaki M, Eguchi H, Nagano H, Yoshimori T, Takehara T. Rubicon inhibits autophagy and accelerates hepatocyte apoptosis and lipid accumulation in nonalcoholic fatty liver disease in mice. Hepatology. 2016 Dec;64(6):1994-2014.<\/li>\n
  11. Hikita H, Kodama T, Tanaka S, Saito Y, Nozaki Y, Nakabori T, Shimizu S, Hayashi Y, Li W, Shigekawa M, Sakamori R, Miyagi T, Hiramatsu N, Tatsumi T, Takehara T. Activation of the Mitochondrial Apoptotic Pathway Produces Reactive Oxygen Species and Oxidative Damage in Hepatocytes That Contribute to Liver Tumorigenesis. Cancer Prev Res (Phila). 2015 Aug;8(8):693-701.<\/li>\n
  12. Kodama T, Hikita H, Kawaguchi T, Saito Y, Tanaka S, Shigekawa M, Shimizu S, Li W, Miyagi T, Kanto T, Hiramatsu N, Tatsumi T, Takehara T. The Bcl-2 homology domain 3 (BH3)-only proteins Bim and bid are functionally active and restrained by anti-apoptotic Bcl-2 family proteins in healthy liver. J Biol Chem. 2013 Oct 18;288(42):30009-30018.<\/li>\n
  13. Hikita H, Kodama T, Shimizu S, Li W, Shigekawa M, Tanaka S, Hosui A, Miyagi T, Tatsumi T, Kanto T, Hiramatsu N, Morii E, Hayashi N, Takehara T. Bak deficiency inhibits liver carcinogenesis: a causal link between apoptosis and carcinogenesis. J Hepatol. 2012 Jul;57(1):92-100.<\/li>\n
  14. Hikita H, Takehara T, Kodama T, Shimizu S, Shigekawa M, Hosui A, Miyagi T, Tatsumi T, Ishida H, Li W, Kanto T, Hiramatsu N, Shimizu S, Tsujimoto Y, Hayashi N. Delayed-onset caspase-dependent massive hepatocyte apoptosis upon Fas activation in Bak\/Bax-deficient mice. Hepatology. 2011 Jul;54(1):240-51.<\/li>\n
  15. Hikita H, Takehara T, Shimizu S, Kodama T, Shigekawa M, Iwase K, Hosui A, Miyagi T, Tatsumi T, Ishida H, Li W, Kanto T, Hiramatsu N, Hayashi N. The Bcl-xL inhibitor, ABT-737, efficiently induces apoptosis and suppresses growth of hepatoma cells in combination with sorafenib. Hepatology. 2010 Oct;52(4):1310-21.<\/li>\n
  16. Shimizu S, Takehara T, Hikita H, Kodama T, Miyagi T, Hosui A, Tatsumi T, Ishida H, Noda T, Nagano H, Doki Y, Mori M, Hayashi N. The let-7 family of microRNAs inhibits Bcl-xL expression and potentiates sorafenib-induced apoptosis in human hepatocellular carcinoma. J Hepatol. 2010 May;52(5):698-704.<\/li>\n
  17. Hikita H, Takehara T, Kodama T, Shimizu S, Hosui A, Miyagi T, Tatsumi T, Ishida H, Ohkawa K, Li W, Kanto T, Hiramatsu N, Hennighausen L, Yin XM, Hayashi N. BH3-only protein bid participates in the Bcl-2 network in healthy liver cells. Hepatology. 2009 Dec;50(6):1972-80.<\/li>\n
  18. Hikita H, Takehara T, Shimizu S, Kodama T, Li W, Miyagi T, Hosui A, Ishida H, Ohkawa K, Kanto T, Hiramatsu N, Yin XM, Hennighausen L, Tatsumi T, Hayashi N. Mcl-1 and Bcl-xL cooperatively maintain integrity of hepatocytes in developing and adult murine liver. Hepatology. 2009 Oct;50(4):1217-26.<\/li>\n
  19. Takehara T, Tatsumi T, Suzuki T, Rucker EB 3rd, Hennighausen L, Jinushi M, Miyagi T, Kanazawa Y, Hayashi N. Hepatocyte-specific disruption of Bcl-xL leads to continuous hepatocyte apoptosis and liver fibrotic responses. Gastroenterology. 2004 Oct;127(4):1189-97.<\/li>\n <\/ol>\n <\/section>\n\n <\/div>\n<\/main>\n","protected":false},"excerpt":{"rendered":"

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