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Hepatic stellate cells secreting WFA + ‐M2BP: Its role in biological interactions with Kupffer cells
Author(s) -
Bekki Yuki,
Yoshizumi Tomoharu,
Shimoda Shinji,
Itoh Shinji,
Harimoto Norifumi,
Ikegami Toru,
Kuno Atsushi,
Narimatsu Hisashi,
Shirabe Ken,
Maehara Yoshihiko
Publication year - 2017
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/jgh.13708
Subject(s) - hepatic stellate cell , cirrhosis , fibrosis , pathology , hepatic fibrosis , biology , liver cytology , medicine , endocrinology , liver metabolism
Background and Aim Hepatic stellate cells (HSCs) play a central role in hepatic fibrosis and are regulated by Kupffer cells (KCs). Wisteria floribunda agglutinin‐positive Mac‐2 binding protein (WFA + ‐M2BP) was recently identified as a serum marker for hepatic fibrosis. Although WFA + ‐M2BP was identified as a ligand of Mac‐2, the function of WFA + ‐M2BP in hepatic fibrosis remains unclear. Methods Liver specimens were obtained from five patients with cirrhosis, five with chronic hepatitis, and five without hepatic fibrosis. WFA + ‐M2BP kinetics were evaluated histologically and in subpopulations of liver cells such as HSCs, KCs, endothelial cells, biliary epithelial cells, and hepatocytes in in vitro culture. The function of WFA + ‐M2BP in activated HSCs was evaluated using immunoblot analysis. Results Numbers of WFA + ‐M2BP‐positive cells in liver tissues increased with fibrosis stage. There were significant differences in WFA + ‐M2BP levels between fibrosis stages F0 and F1–2 ( P = 0.012) and between fibrosis stages F1–2 and F3–4 ( P < 0.001). HSCs were the source of WFA + ‐M2BP secretion in in vitro cultures of liver cells, as determined by sandwich immunoassay. Cells of the human HSC line LX‐2 also secreted WFA + ‐M2BP. Histologically, tissue sections showed that WFA + ‐M2BP was located in Mac‐2‐expressing KCs. In vitro assays showed that exogenous WFA + ‐M2BP stimulation enhanced Mac‐2 expression in KCs and that HSCs co‐cultured with KCs increased α ‐smooth muscle actin expression. Finally, Mac‐2‐depleted KCs with short interfering RNA had reduced α ‐smooth muscle actin expression following co‐culturing with HSCs. Conclusions WFA + ‐M2BP from HSCs induces Mac‐2 expression in KCs, which in turn activates HSCs to be fibrogenic.