World journal of gastroenterology · 2017
STAT3 deficiency prevents hepatocarcinogenesis and promotes biliary proliferation in thioacetamide-induced liver injury.
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Abe Mitsuhiko, Yoshida Takafumi, Akiba Jun, Ikezono Yu, Wada Fumitaka, Masuda Atsutaka, Sakaue Takahiko, Tanaka Toshimitsu, Iwamoto Hideki, Nakamura Toru, Sata Michio, Koga Hironori, Yoshimura Akihiko, Torimura Takuji
Аннотация
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 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.
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 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.
CONCLUSION: STAT3 may regulate hepatocyte proliferation as well as transdifferentiation into cholangiocytes and serve as a therapeutic target for HCC inhibition and biliary regeneration.
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 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.
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 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.
CONCLUSION: STAT3 may regulate hepatocyte proliferation as well as transdifferentiation into cholangiocytes and serve as a therapeutic target for HCC inhibition and biliary regeneration.
Предметные рубрики MeSH
Adaptor Proteins, Signal TransducingAnimalsBiliary TractCarcinogenesisCarcinoma, HepatocellularCell Cycle ProteinsCell ProliferationCell TransdifferentiationChemical and Drug Induced Liver InjuryHepatocytesLiverLiver NeoplasmsLiver Neoplasms, ExperimentalMaleMiceMice, Inbred C57BLMice, TransgenicPhosphoproteinsPhosphorylationRegenerationSOX9 Transcription FactorSTAT3 Transcription FactorThioacetamideUp-RegulationYAP-Signaling Proteins