学位論文 Hepatic stellate cells secrete WFA+-M2BP; its role in biological interactions with Kupffer cells

別城, 悠樹

2017-04-30
内容記述
Background and aims: 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, Kupffer cells, 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 ELISA. 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 exogenous WFA(+) -M2BP stimulation enhanced Mac-2 expression in KCs, and that HSCs co-cultured with KCs increased α-SMA expression. Finally, Mac-2-depleted KCs with siRNA had reduced α-SMA expression following coculture with HSCs. Conclusions: WFA(+) -M2BP from HSCs induces Mac-2 expression in KCs, which in turn activates HSCs to be fibrogenic. Hepatic stellate cells secreting WFA+‐M2BP: Its role in biological interactions... | Request PDF. Available from: https://www.researchgate.net/publication/311898414_Hepatic_stellate_cells_secreting_WFA-M2BP_Its_role_in_biological_interactions_with_Kupffer_cells [accessed Jan 17 2018].
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