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2. The Role of GLI in the Regulation of Hepatic Epithelial–Mesenchymal Transition in Biliary Atresia

Author

Pu Siyu, Wang Junxiang, Wang Qi, Zhang Yimao, and Jin Shuguang

Subjects
biliary atresia, epithelial–mesenchymal transition, Shh signaling pathway, GLI, liver fibrosis, Pediatrics, RJ1-570
Abstract

ObjectiveTo study the regulatory role of GLI1/GLI2, a nuclear transcription factor of the Sonic hedgehog (Shh) signaling pathway, in epithelial–mesenchymal transition (EMT) related to hepatic fibrosis in patients with biliary atresia (BA).MethodsThe messenger RNA (mRNA) and protein expression levels of GLI1/GLI2, Snail/Slug, and other Shh- and EMT-related cytokines were tested in the liver tissues of BA patients and animals. Then, GLI1/GLI2 was silenced and overexpressed in mouse intrahepatic bile duct epithelial cells (mIBECs) and BA animals to investigate changes in the mRNA and protein expression of EMT key factors and liver fibrosis indicators. After silencing and overexpression of GLI1/GLI2, immunofluorescence was used to detect the expression of cytokeratin-19 (CK19) and α-smooth muscle actin (α-SMA) in mIBECs, and hematoxylin and eosin (HE) staining and Masson staining were used to observe the degree of liver fibrosis in the BA animals.ResultsCompared with the control, the mRNA and protein expression levels of GLI2, Snail, vimentin, and α-SMA were significantly increased and those of E-cadherin were significantly decreased in liver tissue from BA patients and animals. Overexpression of GLI2 increased the mRNA and protein expression levels of Snail, vimentin, and α-SMA and that of E-cadherin was significantly decreased in mIBECs and BA animals. After GLI2 silencing, the opposite pattern was observed. Immunofluorescence detection showed enhanced expression of the bile duct epithelial cell marker CK19 in mIBECs after GLI2 silencing and enhanced expression of the mesenchymal cell marker α-SMA after GLI2 overexpression. HE and Masson staining suggested that the GLI2-overexpressing group had a significantly higher degree of fibrosis.ConclusionThe Shh signaling pathway plays an important role in fibrogenesis in BA. GLI2 can significantly regulate EMT in mIBECs and livers of BA mice.

Published
2022
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8. Additional file 1 of Liver transplantation in a child with liver cirrhosis caused by langerhans cell histiocytosis: a case report

Author

Wang, Qi, Jin, Shuguang, Xiang, Bo, and Chen, Jing

Abstract

Additional file 1: Figure S1. Hematoxylin and eosin staining of liver biopsy.��� the damage and regeneration of liver cells and pseudolobule formation. ��� dilation of portal area, proliferation of fibrous tissue and small bile duct. ��� infiltration of inflammation cells. Figure S2. The changes of liver function in this LCH patient. The patient was found to have an abnormal liver function at 20 months old, and was referred to our hospital at 25 months old. Then the living-donor liver transplantation was perfomed when he was 27 months old. ALT: alanine aminotransferase; AST: aspartate aminotransferase; PT: prothrombin time; TB: total bilirubin; ALB: albumin. Figure S3. Macroscopic appearance of the recipient���s liver. a The diaphragmatic surface of liver. b The visceral surface of liver. Figure S4. The enhanced CT of the chest and ultrasound examination of the liver. a-b: the enhanced CT of the chest was performed when the patient was 39 months old and the results were normal; c-d: the ultrasound examination of the liver was performed regularly every 3-6 month since the liver transplantation, and the results were all shown that the echo of the transplanted liver parenchyma was uniform and no dilation of the intrahepatic biliary tract was observed, the presented images were performed when the patient was 45 months old.

Published
2022
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