A Potential Profibrogenic Role of Biliary Epithelium-Derived Cardiotrophin-1 in Pediatric Cholestatic Liver Disease.
As a cytokine of the interleukin-6 family, cardiotrophin-1 (CT-1) has been shown to be an important endogenous protector in liver injury. Our study aimed to investigate the role of CT-1 in liver fibrosis in pediatric cholestatic liver disease (PCLD). CT-1 mRNA and protein expression levels were upregulated in PCLD liver biopsy tissues compared with controls. Immunohistochemistry and confocal microscopy of liver sections showed that CT-1 was predominantly expressed by biliary epithelium cells. Serum CT-1 was elevated significantly in the children with PCLD compared with controls. Serum CT-1 levels exhibited a moderate positive correlation with the Scheuer stage of hepatic fibrosis and serum TB levels and a weak correlation with serum ALP levels. In vitro analysis indicated that LX-2 cells preconditioned with CT-1 exhibited significant increments in proliferation and accumulation of extracellular matrix components, while also positively regulating the STAT3 and p38MAPK pathways. In conclusion, biliary epithelium-derived CT-1 may exert a profibrogenic potential in PCLD.
1 Department of Liver Surgery and Liver Transplantation Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai, People's Republic of China .
Xiangwei
X
Hua
1 Department of Liver Surgery and Liver Transplantation Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai, People's Republic of China .
Yuhua
Y
Shan
1 Department of Liver Surgery and Liver Transplantation Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai, People's Republic of China .
Dawei
D
Li
1 Department of Liver Surgery and Liver Transplantation Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai, People's Republic of China .
Dongwei
D
Xu
1 Department of Liver Surgery and Liver Transplantation Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai, People's Republic of China .
Jiang
J
Zhang
1 Department of Liver Surgery and Liver Transplantation Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai, People's Republic of China .
Taihua
T
Yang
1 Department of Liver Surgery and Liver Transplantation Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai, People's Republic of China .
Longzhi
L
Han
1 Department of Liver Surgery and Liver Transplantation Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai, People's Republic of China .
Conghuan
C
Shen
1 Department of Liver Surgery and Liver Transplantation Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai, People's Republic of China .
Yun
Y
Xia
2 Department of Urology, Shanghai Children's Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine , Shanghai, People's Republic of China .
Qimin
Q
Chen
3 Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai Institute of Digestive Disease, Shanghai, People's Republic of China .|4 Key Laboratory of Gastroenterology & Hepatology, Ministry of Health (Shanghai Jiao-Tong University) , Shanghai, People's Republic of China .
Xiong
X
Ma
1 Department of Liver Surgery and Liver Transplantation Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai, People's Republic of China .
Jianjun
J
Zhang
1 Department of Liver Surgery and Liver Transplantation Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai, People's Republic of China .
Qiang
Q
Xia
D000328:Adult; D001653:Bile Ducts, Intrahepatic / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D002648:Child; D002780:Cholestasis, Intrahepatic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D016207:Cytokines / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007223:Infant; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008105:Liver Cirrhosis, Biliary / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008111:Liver Function Tests; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D055815:Young Adult; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D016207:Cytokines; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; C092073:cardiotrophin 1; D048051:p38 Mitogen-Activated Protein Kinases