{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T03:27:04Z","timestamp":1787887624200,"version":"build-2784847793"},"reference-count":22,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2017,6,22]],"date-time":"2017-06-22T00:00:00Z","timestamp":1498089600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Gastro and Hepatol"],"published-print":{"date-parts":[[2017,7]]},"abstract":"Abstract<\/jats:title>\n \n Background and Aim<\/jats:title>\n \n Hepatic stellate cells (HSCs) play a central role in hepatic fibrosis and are regulated by Kupffer cells (KCs).\n \n Wisteria floribunda<\/jats:italic>\n <\/jats:styled-content>\n agglutinin\u2010positive Mac\u20102 binding protein (WFA\n +<\/jats:sup>\n \u2010M2BP) was recently identified as a serum marker for hepatic fibrosis. Although WFA\n +<\/jats:sup>\n \u2010M2BP was identified as a ligand of Mac\u20102, the function of WFA\n +<\/jats:sup>\n \u2010M2BP in hepatic fibrosis remains unclear.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Liver specimens were obtained from five patients with cirrhosis, five with chronic hepatitis, and five without hepatic fibrosis. WFA\n +<\/jats:sup>\n \u2010M2BP kinetics were evaluated histologically and in subpopulations of liver cells such as HSCs, KCs, endothelial cells, biliary epithelial cells, and hepatocytes in\n in vitro<\/jats:italic>\n culture. The function of WFA\n +<\/jats:sup>\n \u2010M2BP in activated HSCs was evaluated using immunoblot analysis.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Numbers of WFA\n +<\/jats:sup>\n \u2010M2BP\u2010positive cells in liver tissues increased with fibrosis stage. There were significant differences in WFA\n +<\/jats:sup>\n \u2010M2BP levels between fibrosis stages F0 and F1\u20132 (\n P<\/jats:italic>\n \u00a0=\u00a00.012) and between fibrosis stages F1\u20132 and F3\u20134 (\n P<\/jats:italic>\n \u00a0<\u00a00.001). HSCs were the source of WFA\n +<\/jats:sup>\n \u2010M2BP secretion in\n in vitro<\/jats:italic>\n cultures of liver cells, as determined by sandwich immunoassay. Cells of the human HSC line LX\u20102 also secreted WFA\n +<\/jats:sup>\n \u2010M2BP. Histologically, tissue sections showed that WFA\n +<\/jats:sup>\n \u2010M2BP was located in Mac\u20102\u2010expressing KCs.\n In vitro<\/jats:italic>\n assays showed that exogenous WFA\n +<\/jats:sup>\n \u2010M2BP stimulation enhanced Mac\u20102 expression in KCs and that HSCs co\u2010cultured with KCs increased\n \u03b1<\/jats:italic>\n \u2010smooth muscle actin expression. Finally, Mac\u20102\u2010depleted KCs with short interfering RNA had reduced\n \u03b1<\/jats:italic>\n \u2010smooth muscle actin expression following co\u2010culturing with HSCs.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n WFA\n +<\/jats:sup>\n \u2010M2BP from HSCs induces Mac\u20102 expression in KCs, which in turn activates HSCs to be fibrogenic.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/jgh.13708","type":"journal-article","created":{"date-parts":[[2016,12,24]],"date-time":"2016-12-24T10:09:13Z","timestamp":1482574153000},"page":"1387-1393","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":87,"title":["Hepatic stellate cells secreting WFA\n +<\/sup>\n \u2010M2BP: Its role in biological interactions with Kupffer cells"],"prefix":"10.1111","volume":"32","author":[{"given":"Yuki","family":"Bekki","sequence":"first","affiliation":[{"name":"Department of Surgery and Science Graduate School of Medical Sciences, Kyushu University Higashi\u2010ku Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoharu","family":"Yoshizumi","sequence":"additional","affiliation":[{"name":"Department of Surgery and Science Graduate School of Medical Sciences, Kyushu University Higashi\u2010ku Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinji","family":"Shimoda","sequence":"additional","affiliation":[{"name":"Department of Medicine and Biosystemic Science Graduate School of Medical Sciences, Kyushu University Higashi\u2010ku Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinji","family":"Itoh","sequence":"additional","affiliation":[{"name":"Department of Surgery and Science Graduate School of Medical Sciences, Kyushu University Higashi\u2010ku Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norifumi","family":"Harimoto","sequence":"additional","affiliation":[{"name":"Department of Surgery and Science Graduate School of Medical Sciences, Kyushu University Higashi\u2010ku Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toru","family":"Ikegami","sequence":"additional","affiliation":[{"name":"Department of Surgery and Science Graduate School of Medical Sciences, Kyushu University Higashi\u2010ku Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Kuno","sequence":"additional","affiliation":[{"name":"Research Center for Medical Glycoscience (RCMG) National Institute of Advanced Industrial Science and Technology (AIST) Tsukuba Ibaraki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisashi","family":"Narimatsu","sequence":"additional","affiliation":[{"name":"Research Center for Medical Glycoscience (RCMG) National Institute of Advanced Industrial Science and Technology (AIST) Tsukuba Ibaraki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken","family":"Shirabe","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Surgery Gunma University Maebashi Gunma Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiko","family":"Maehara","sequence":"additional","affiliation":[{"name":"Department of Surgery and Science Graduate School of Medical Sciences, Kyushu University Higashi\u2010ku Fukuoka 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