Hepatic stellate cells secreting WFA+-M2BP: Its role in biological interactions with Kupffer cells

Yuki Bekki, Tomoharu Yoshizumi, Shinji Shimoda, Shinji Itoh, Norifumi Harimoto, Toru Ikegami, Atsushi Kuno, Hisashi Narimatsu, Ken Shirabe, Yoshihiko Maehara

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70 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1387-1393
Number of pages7
JournalJournal of Gastroenterology and Hepatology (Australia)
Issue number7
Publication statusPublished - Jul 2017

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Gastroenterology


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