原发性胆汁性胆管炎肝内胆管上皮细胞TLR4及上皮-间质转化相关标志物的表达

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Abstract Objective: To explore the expression levels of Toll-like receptor 4 (TLR4) and epithelial-mesenchymal transition (EMT)-related markers in intrahepatic biliary epithelial cells (IBEC) and their association in patients with primary biliary cholangitis (PBC). Methods: Immunohistochemistry assay was used to detect the expression levels of TLR4 and EMT-related markers (E-cadherin and vimentin) in IBEC from liver tissues of 11 PBC patients and 5 healthy controls (donors for liver transplantation) from Shanghai Changzheng Hospital. The correlations between TLR4, EMT and PBC fibrosis progression were analyzed. Results: No expression of TLR4 was observed in IBEC of healthy individuals, while significant expression was found in PBC patients. The positive ratios of TLR4 in PBC patients were 28.6%, 41.6%, 64.0% and 73.1% in stage 1, 2, 3 and 4, respectively. The differences were statistically significant between stages except for stage 1 vs. 2 and stage 3 vs. 4 (P<0.01). The expression level of E-cadherin was significantly decreased in IBEC of PBC patients, compared with that of healthy individuals. The positive ratios of E-cadherin were 84.0%, 8.1%, 23.0% and 19.0% respectively in stage 1, 2, 3 and 4 in PBC patients. The differences were statistically significant between groups except for healthy group vs. stage 1 and stage 3 vs. 4 (P<0.01). There was no expression of vimentin in IBEC of healthy individuals, while significant expression in PBC patients. The positive ratios of vimentin were 30.0%, 40.1%, 73.7% and 77.0%, respectively in stage 1, 2, 3 and 4 in PBC patients. There were statistically significant differences between stages except stage 1 vs. 2 and stage 3 vs. 4 (P<0.01). The positive ratio of TLR4 in IBEC had significant negative correlation with that of E-cadherin (r=-0.927, P<0.001), but positively related to that of vimentin (r=0.918, P<0.001). Additionally, the positive ratio of E-cadherin had also significant negative association with that of vimentin (r= -0.918, P<0.001). Conclusion: The expression of TLR4 is increased and EMT occurs in IBEC of PBC patients. Furthermore, TLR4 is closely associated with EMT and both of them show close correlation with PBC fibrosis progression.

Key words： Toll-like receptor 4 epithelial-mesenchymal transition primary biliary cholangitis immuno-histochemistry

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	LIU Donghong
	LIN Feng
	YANG Zaixing
	ZHANG Zhencheng
	ZHONG Renqian
	LIANG Yan

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https://xb.wmu.edu.cn/EN/ OR https://xb.wmu.edu.cn/EN/Y2018/V48/I8/567

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