Fn14 hepatic progenitor cells are associated with liver fibrosis in biliary atresia.
OBJECTIVE
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 BAband BAagroup.


CONCLUSIONS
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.
Department of Pediatric Surgery, Shanghai Children's Hospital, Shanghai Jiao Tong University, No. 355 Luding Road, Shanghai, 200062, China.
Lulu
L
Zheng
Department of Pediatric Surgery, Shanghai Children's Hospital, Shanghai Jiao Tong University, No. 355 Luding Road, Shanghai, 200062, China. lvzhibao1@163.com.
Zhibao
Z
Lv
Department of Pediatric Surgery, Shanghai Children's Hospital, Shanghai Jiao Tong University, No. 355 Luding Road, Shanghai, 200062, China.
Zhenhua
Z
Gong
Department of Pediatric Surgery, Shanghai Children's Hospital, Shanghai Jiao Tong University, No. 355 Luding Road, Shanghai, 200062, China.
Qingfeng
Q
Sheng
Department of Center Laboratory, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, 200062, China.
Zhimei
Z
Gao
Department of Pediatric Surgery, Shanghai Children's Hospital, Shanghai Jiao Tong University, No. 355 Luding Road, Shanghai, 200062, China.
Yuting
Y
Zhang
Department of Pediatric Surgery, Shanghai Children's Hospital, Shanghai Jiao Tong University, No. 355 Luding Road, Shanghai, 200062, China.
Shenghua
S
Yu
Department of Pediatric Surgery, Shanghai Children's Hospital, Shanghai Jiao Tong University, No. 355 Luding Road, Shanghai, 200062, China.
Junmei
J
Zhou
Department of Pathology, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, 200062, China.
Zhengjun
Z
Xi
Department of Pathology, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, 200062, China.
Xueli
X
Wang
D000293:Adolescent; D001656:Biliary Atresia / Q000150:complications* / Q000378:metabolism* / Q000601:surgery; D015415:Biomarkers / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007223:Infant; D008099:Liver / Q000378:metabolism; D008103:Liver Cirrhosis / Q000150:complications* / Q000235:genetics / Q000378:metabolism*; D008111:Liver Function Tests; D008297:Male; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism*; D013234:Stem Cells / Q000378:metabolism*; D000074050:TWEAK Receptor
D015415:Biomarkers; D018124:Receptors, Tumor Necrosis Factor; C000613297:TNFRSF12A protein, human; D000074050:TWEAK Receptor
Biliary atresia; Fn14+ cells; HPCs; Liver fibrosis; α-SMA+ cells