STAT3 deficiency prevents hepatocarcinogenesis and promotes biliary proliferation in thioacetamide-induced liver injury.
STAT3 deficiency prevents hepatocarcinogenesis and promotes biliary proliferation in thioacetamide-induced liver injury.
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DOI：
10.3748/wjg.v23.i37.6833
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发表时间：
2017-10-07
影响因子：
4.3
通讯作者：
Torimura T
中科院分区：
文献类型：
--
作者：
Abe M;Yoshida T;Akiba J;Ikezono Y;Wada F;Masuda A;Sakaue T;Tanaka T;Iwamoto H;Nakamura T;Sata M;Koga H;Yoshimura A;Torimura T
探讨STAT3在慢性肝损伤后肝癌发生和胆管增生中的作用。我们研究了硫代乙酰胺（TAA）诱导的肝损伤，代偿性肝细胞增殖，肝细胞癌（HCC）的发展在肝STAT3缺陷小鼠。此外，我们评估了TAA诱导的胆管增殖，并分析了性别决定区Y盒9（SOX 9）和Yes相关蛋白（雅普）的激活，这些蛋白调节肝细胞向胆管细胞的转分化。与对照小鼠相比，肝脏STAT3缺陷小鼠的代偿性肝细胞增殖和HCC形成均显著减少。STAT3缺陷导致肝坏死和纤维化加重。另一方面，与对照肝脏相比，肝脏STAT3缺陷肝脏中的胆管增殖增加。SOX 9和雅普在肝STAT 3缺陷肝细胞中上调。STAT3可以调节肝细胞增殖以及向胆管细胞的转分化，并作为HCC抑制和胆管再生的治疗靶点。
To elucidate the role of STAT3 in hepatocarcinogenesis and biliary ductular proliferation following chronic liver injury. We investigated thioacetamide (TAA)-induced liver injury, compensatory hepatocyte proliferation, and hepatocellular carcinoma (HCC) development in hepatic STAT3-deficient mice. In addition, we evaluated TAA-induced biliary ductular proliferation and analyzed the activation of sex determining region Y-box9 (SOX9) and Yes-associated protein (YAP), which regulate the transdifferentiation of hepatocytes to cholangiocytes. Both compensatory hepatocyte proliferation and HCC formation were significantly decreased in hepatic STAT3-deficient mice as compared with control mice. STAT3 deficiency resulted in augmentation of hepatic necrosis and fibrosis. On the other hand, biliary ductular proliferation increased in hepatic STAT3-deficient livers as compared with control livers. SOX9 and YAP were upregulated in hepatic STAT3-deficient hepatocytes. STAT3 may regulate hepatocyte proliferation as well as transdifferentiation into cholangiocytes and serve as a therapeutic target for HCC inhibition and biliary regeneration.
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DOI：
10.1083/jcb.200108066
发表时间：
2002-01-07
期刊：
The Journal of cell biology
影响因子：
--
作者：
Suzuki A;Zheng YW;Kaneko S;Onodera M;Fukao K;Nakauchi H;Taniguchi H
通讯作者：
Taniguchi H
DOI：
10.1073/pnas.96.6.2846
发表时间：
1999-03-16
影响因子：
11.1
作者：
Raz, R;Lee, CK;Levy, DE
通讯作者：
Levy, DE
影响因子：
64.8
作者：
Taniguchi, Koji;Wu, Li-Wha;Grivennikov, Sergei I.;de Jong, Petrus R.;Lian, Ian;Yu, Fa-Xing;Wang, Kepeng;Ho, Samuel B.;Boland, Brigid S.;Chang, John T.;Sandborn, William J.;Hardiman, Gary;Raz, Eyal;Maehara, Yoshihiko;Yoshimura, Akihiko;Zucman-Rossi, Jessica;Guan, Kun-Liang;Karin, Michael
通讯作者：
Karin, Michael
影响因子：
64.5
作者：
Rosenbluh J;Nijhawan D;Cox AG;Li X;Neal JT;Schafer EJ;Zack TI;Wang X;Tsherniak A;Schinzel AC;Shao DD;Schumacher SE;Weir BA;Vazquez F;Cowley GS;Root DE;Mesirov JP;Beroukhim R;Kuo CJ;Goessling W;Hahn WC
通讯作者：
Hahn WC
影响因子：
13.5
作者：
Bai, Haibo;Zhang, Nailing;Xu, Yang;Chen, Qian;Khan, Mehtab;Potter, James J.;Nayar, Suresh K.;Cornish, Toby;Alpini, Gianfranco;Bronk, Steven;Pan, Duojia;Anders, Robert A.
通讯作者：
Anders, Robert A.