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

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

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)
Volume32
Issue number7
DOIs
Publication statusPublished - Jul 2017

Fingerprint

Hepatic Stellate Cells
Kupffer Cells
Fibrosis
Liver
Smooth Muscle
Actins
Chronic Hepatitis
Immunoassay
Small Interfering RNA
Hepatocytes
Carrier Proteins
Endothelial Cells
Cell Culture Techniques
Biomarkers
Epithelial Cells
Ligands
Cell Line

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Gastroenterology

Cite this

Hepatic stellate cells secreting WFA+-M2BP : Its role in biological interactions with Kupffer cells. / Bekki, Yuki; Yoshizumi, Tomoharu; Shimoda, Shinji; Itoh, Shinji; Harimoto, Norifumi; Ikegami, Toru; Kuno, Atsushi; Narimatsu, Hisashi; Shirabe, Ken; Maehara, Yoshihiko.

In: Journal of Gastroenterology and Hepatology (Australia), Vol. 32, No. 7, 07.2017, p. 1387-1393.

Research output: Contribution to journalArticle

Bekki, Yuki ; Yoshizumi, Tomoharu ; Shimoda, Shinji ; Itoh, Shinji ; Harimoto, Norifumi ; Ikegami, Toru ; Kuno, Atsushi ; Narimatsu, Hisashi ; Shirabe, Ken ; Maehara, Yoshihiko. / Hepatic stellate cells secreting WFA+-M2BP : Its role in biological interactions with Kupffer cells. In: Journal of Gastroenterology and Hepatology (Australia). 2017 ; Vol. 32, No. 7. pp. 1387-1393.
@article{8b11be6c69a04e73aea776aa30f8f3d3,
title = "Hepatic stellate cells secreting WFA+-M2BP: Its role in biological interactions with Kupffer cells",
abstract = "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.",
author = "Yuki Bekki and Tomoharu Yoshizumi and Shinji Shimoda and Shinji Itoh and Norifumi Harimoto and Toru Ikegami and Atsushi Kuno and Hisashi Narimatsu and Ken Shirabe and Yoshihiko Maehara",
year = "2017",
month = "7",
doi = "10.1111/jgh.13708",
language = "English",
volume = "32",
pages = "1387--1393",
journal = "Journal of Gastroenterology and Hepatology (Australia)",
issn = "0815-9319",
publisher = "Wiley-Blackwell",
number = "7",

}

TY - JOUR

T1 - Hepatic stellate cells secreting WFA+-M2BP

T2 - Its role in biological interactions with Kupffer cells

AU - Bekki, Yuki

AU - Yoshizumi, Tomoharu

AU - Shimoda, Shinji

AU - Itoh, Shinji

AU - Harimoto, Norifumi

AU - Ikegami, Toru

AU - Kuno, Atsushi

AU - Narimatsu, Hisashi

AU - Shirabe, Ken

AU - Maehara, Yoshihiko

PY - 2017/7

Y1 - 2017/7

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85021167813&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85021167813&partnerID=8YFLogxK

U2 - 10.1111/jgh.13708

DO - 10.1111/jgh.13708

M3 - Article

C2 - 28008658

AN - SCOPUS:85021167813

VL - 32

SP - 1387

EP - 1393

JO - Journal of Gastroenterology and Hepatology (Australia)

JF - Journal of Gastroenterology and Hepatology (Australia)

SN - 0815-9319

IS - 7

ER -