| Expression and functional analysis of endoglin in isolated liver cells and its involvement in fibrogenic Smad signalling. | |
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MedLine Citation:
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PMID: 21146604 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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Endoglin is an accessory component of the TGF-β-binding receptor complex that differentially modulates TGF-β and BMP responses. The existence of two splice variants L- and S-endoglin which differ in their cytoplasmic domain has already been shown in human and mice. Endoglin is located on the cell surfaces of cultured hepatic stellate cells and transdifferentiated myofibroblasts suggesting that this receptor might be associated with the profibrogenic attributes of these liver cell subpopulations. We now show that endoglin expression is increased in transdifferentiating hepatic stellate cells and in two models of liver fibrosis (i.e. bile duct ligation and carbon tetrachloride model) and further detectable in cultured portal fibroblasts representing another important fibrogenic cell type but not in hepatocytes. In respect to TGF-β1-signalling, we demonstrate that endoglin interacts with and is phosphorylated by TβRII. In hepatic stellate cells, TGF-β1 upregulates endoglin expression most likely via the ALK5 pathway and requires the SP1 transcription factor. We further identified a novel rat splice variant that is structurally and functionally different from that identified in human and mouse. Transient overexpression of endoglin resulted in a strong increase of TGF-β1-driven Smad1/5 phosphorylation and α-smooth muscle actin expression in a hepatic stellate cell line. In supernatants of respective cultures, we could detect the ectodomain of endoglin suggesting that shedding is a further key process involved in the regulation of this surface receptor. |
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Authors:
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Steffen K Meurer; Lidia Tihaa; Erawan Borkham-Kamphorst; Ralf Weiskirchen |
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Publication Detail:
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Type: Journal Article Date: 2010-12-10 |
Journal Detail:
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Title: Cellular signalling Volume: 23 ISSN: 1873-3913 ISO Abbreviation: Cell. Signal. Publication Date: 2011 Apr |
Date Detail:
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Created Date: 2011-01-31 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8904683 Medline TA: Cell Signal Country: England |
Other Details:
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Languages: eng Pagination: 683-99 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier Inc. All rights reserved. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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