Lulu Zheng1, Zhibao Lv2, Zhenhua Gong1, Qingfeng Sheng1, Zhimei Gao3, Yuting Zhang1, Shenghua Yu1, Junmei Zhou1, Zhengjun Xi4, Xueli Wang4. 1. Department of Pediatric Surgery, Shanghai Children's Hospital, Shanghai Jiao Tong University, No. 355 Luding Road, Shanghai, 200062, China. 2. Department of Pediatric Surgery, Shanghai Children's Hospital, Shanghai Jiao Tong University, No. 355 Luding Road, Shanghai, 200062, China. lvzhibao1@163.com. 3. Department of Center Laboratory, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, 200062, China. 4. Department of Pathology, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, 200062, China.
Abstract
PURPOSE: The liver in biliary atresia (BA) is characterized by progressing fibrosis which is promoted by unclear reasons. We aimed to understand the factors influencing liver fibrosis. This study hypothesized that HPCs (hepatic progenitor cells) are activated and associated with liver fibrosis in biliary atresia. METHODS: Liver samples from biliary atresia patients are as BA group, and the normal liver derived from hepatoblastoma infants during operation are control group. The extent of fibrosis in liver samples was blindly evaluated by two experienced pathologists depending on Ishak system. The BA liver samples were divided into mild liver fibrosis group (grade I-IV, BAa) and severe liver fibrosis group (grade V-VI, BAb) to detect Fn14 protein expression. RESULTS: In mRNA level, Fn14 expression was 21.23 ± 8.3 vs. 1.00 ± 0.17, p = 0.023 < 0.05 and CD133 expression was 6.02 ± 2.16 vs. 1.14 ± 0.75, p = 0.008 < 0.01 between BA group and control group. Fn14 cells co-expressed the progenitor marker CD133 in liver, and activated in BA. Fn14 andα-SMA were co-location in fibrous area in liver. Compared to the control group, Fn14, CD133, and α-SMA protein expression were 2.10 ± 0.53 vs. 0.97 ± 0.2, p = 0.001, 2.23 ± 0.57 vs. 1.00 ± 0.03, p = 0.000, 4.96 ± 2.4 vs. 1.00 ± 0.22, p = 0.001. The Fn14 protein expression was 2.60 ± 0.35 vs. 1.86 ± 0.42, p = 0.012, between BAb and BAa group. CONCLUSION: Fn14 cells, which co-express the progenitor marker CD133 in liver, are HPCs and activated in BA. Fn14 + HPCs are associated with liver fibrosis in BA.
PURPOSE: The liver in biliary atresia (BA) is characterized by progressing fibrosis which is promoted by unclear reasons. We aimed to understand the factors influencing liver fibrosis. This study hypothesized that HPCs (hepatic progenitor cells) are activated and associated with liver fibrosis in biliary atresia. METHODS: Liver samples from biliary atresiapatients are as BA group, and the normal liver derived from hepatoblastomainfants during operation are control group. The extent of fibrosis in liver samples was blindly evaluated by two experienced pathologists depending on Ishak system. The BA liver samples were divided into mild liver fibrosis group (grade I-IV, BAa) and severe liver fibrosis group (grade V-VI, BAb) to detect Fn14 protein expression. RESULTS: In mRNA level, Fn14 expression was 21.23 ± 8.3 vs. 1.00 ± 0.17, p = 0.023 < 0.05 and CD133 expression was 6.02 ± 2.16 vs. 1.14 ± 0.75, p = 0.008 < 0.01 between BA group and control group. Fn14 cells co-expressed the progenitor marker CD133 in liver, and activated in BA. Fn14 andα-SMA were co-location in fibrous area in liver. Compared to the control group, Fn14, CD133, and α-SMA protein expression were 2.10 ± 0.53 vs. 0.97 ± 0.2, p = 0.001, 2.23 ± 0.57 vs. 1.00 ± 0.03, p = 0.000, 4.96 ± 2.4 vs. 1.00 ± 0.22, p = 0.001. The Fn14 protein expression was 2.60 ± 0.35 vs. 1.86 ± 0.42, p = 0.012, between BAb and BAa group. CONCLUSION:Fn14 cells, which co-express the progenitor marker CD133 in liver, are HPCs and activated in BA. Fn14 + HPCs are associated with liver fibrosis in BA.
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