Fn14 hepatic progenitor cells are associated with liver fibrosis in biliary atresia

Pediatr Surg Int. 2017 May;33(5):593-599. doi: 10.1007/s00383-017-4068-5. Epub 2017 Feb 8.

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.

Keywords: Biliary atresia; Fn14+ cells; HPCs; Liver fibrosis; α-SMA+ cells.

MeSH terms

  • Adolescent
  • Biliary Atresia / complications*
  • Biliary Atresia / metabolism*
  • Biliary Atresia / surgery
  • Biomarkers / metabolism
  • Child
  • Child, Preschool
  • Humans
  • Infant
  • Liver / metabolism
  • Liver Cirrhosis / complications*
  • Liver Cirrhosis / genetics
  • Liver Cirrhosis / metabolism*
  • Liver Function Tests
  • Male
  • Receptors, Tumor Necrosis Factor / genetics
  • Receptors, Tumor Necrosis Factor / metabolism*
  • Stem Cells / metabolism*
  • TWEAK Receptor

Substances

  • Biomarkers
  • Receptors, Tumor Necrosis Factor
  • TNFRSF12A protein, human
  • TWEAK Receptor