Overexpression of Endoglin Modulates TGF-β1-Signalling Pathways in a Novel Immortalized Mouse Hepatic Stellate Cell Line

• DOI: 10.1371/journal.pone.0056116
• Publication Date: 2013-02-20T23:09:01Z
• Authors: Steffen K. Meurer; Muhammad Alsamman; Hacer Sahin; Hermann E. Wasmuth; Tatiana Kisseleva; David A. Brenner; Christian Trautwein; Ralf Weiskirchen; David Scholten
• Keywords: Hepatic stellate cell

Hepatic stellate cells (HSCs) play a major role in the pathogenesis of liver fibrosis. Working on primary HSCs requires difficult isolation procedures; therefore we have generated and here characterize mouse hepatic cell line expressing GFP under control collagen 1(I) promoter/enhancer. These are responsive to pro-fibrogenic stimuIi, such as PDGF or TGF-β1, able activate intracellular signalling pathways including Smads MAP kinases. Nevertheless, due basal level activation, TGF-β1 did not significantly induce expression contrasting regulated endogenous I expression. We could demonstrate that accessory TGF-β-receptor endoglin, which is endogenously expressed at very low levels, has differential effect these when transiently overexpressed. In presence endoglin activation Smad1/5/8 was drastically enhanced. Moreover, phosphorylation ERK1/2 increased, vimentin, α-smooth muscle actin connective tissue growth factor upregulated. Endoglin induced slight increase inhibitor differentiation-2 while amount type reduced. Therefore, this profibrogenic with origin only promising novel experimental tool, can be used vivo for tracing experiments. Furthermore it allows investigating impact various regulatory proteins (e.g. endoglin) signal transduction, differentiation biology.