TY - JOUR
T1 - STAT3 defciency prevents hepatocarcinogenesis and promotes biliary proliferation in thioacetamide-induced liver injury
AU - Abe, Mitsuhiko
AU - Yoshida, Takafumi
AU - Akiba, Jun
AU - Ikezono, Yu
AU - Wada, Fumitaka
AU - Masuda, Atsutaka
AU - Sakaue, Takahiko
AU - Tanaka, Toshimitsu
AU - Iwamoto, Hideki
AU - Nakamura, Toru
AU - Sata, Michio
AU - Koga, Hironori
AU - Yoshimura, Akihiko
AU - Torimura, Takuji
PY - 2017/10/7
Y1 - 2017/10/7
N2 - Aim To elucidate the role of STAT3 in hepatocarcinogenesis and biliary ductular proliferation following chronic liver injury. METHODS We investigated thioacetamide (TAA)-induced liver injury, compensatory hepatocyte proliferation, and hepatocellular carcinoma (HCC) development in hepatic STAT3-deficient mice. In addition, we evaluated TAAinduced 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. RESULTS 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 fbrosis. On the other hand, biliary ductular proliferation increased in hepatic STAT3-defcient livers as compared with control livers. SOX9 and YAP were upregulated in hepatic STAT3-defcient hepatocytes. CONCLUSION STAT3 may regulate hepatocyte proliferation as well as transdifferentiation into cholangiocytes and serve as a therapeutic target for HCC inhibition and biliary regeneration.
AB - Aim To elucidate the role of STAT3 in hepatocarcinogenesis and biliary ductular proliferation following chronic liver injury. METHODS We investigated thioacetamide (TAA)-induced liver injury, compensatory hepatocyte proliferation, and hepatocellular carcinoma (HCC) development in hepatic STAT3-deficient mice. In addition, we evaluated TAAinduced 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. RESULTS 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 fbrosis. On the other hand, biliary ductular proliferation increased in hepatic STAT3-defcient livers as compared with control livers. SOX9 and YAP were upregulated in hepatic STAT3-defcient hepatocytes. CONCLUSION STAT3 may regulate hepatocyte proliferation as well as transdifferentiation into cholangiocytes and serve as a therapeutic target for HCC inhibition and biliary regeneration.
KW - Ductular reaction
KW - Hepatocellular carcinoma
KW - Sex determining region Y-box9
KW - Signal transducer and activator of transcription 3
KW - Transdifferentiation
KW - Yesassociated protein
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U2 - 10.3748/wjg.v23.i37.6833
DO - 10.3748/wjg.v23.i37.6833
M3 - Article
C2 - 29085226
AN - SCOPUS:85030121677
VL - 23
SP - 6833
EP - 6844
JO - World Journal of Gastroenterology
JF - World Journal of Gastroenterology
SN - 1007-9327
IS - 37
ER -