Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 6833-6844 |
| Number of pages | 12 |
| Journal | World Journal of Gastroenterology |
| Volume | 23 |
| Issue number | 37 |
| DOIs | |
| Publication status | Published - 2017 Oct 7 |
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Keywords
- Ductular reaction
- Hepatocellular carcinoma
- Sex determining region Y-box9
- Signal transducer and activator of transcription 3
- Transdifferentiation
- Yesassociated protein
ASJC Scopus subject areas
- Gastroenterology
Cite this
STAT3 defciency prevents hepatocarcinogenesis and promotes biliary proliferation in thioacetamide-induced liver injury. / 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.
In: World Journal of Gastroenterology, Vol. 23, No. 37, 07.10.2017, p. 6833-6844.Research output: Contribution to journal › Article
}
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
UR - http://www.scopus.com/inward/record.url?scp=85030121677&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85030121677&partnerID=8YFLogxK
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 -