Soluble Endoglin modulates TGF-β1 mediated signaling in isolated hepatocytes

Meurer, Steffen K.; Rizk, Mohamed; Tihaa, Lidia; Weiskirchen, Ralf; Gressner, A. M.

doi:10.1055/s-2008-1037544

Cited by 1 publication

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“…Cloning of recombinant adenoviruses for the expression of FL-Eng and sol-Eng was done in the AdEasy-1 system [37]. In brief, the respective cDNA fragments of FL- (2230 bp) and sol-Eng (1789 bp) included in vectors pcDNA3.1-FL-Endoglin [35] and pcDNA3.1-sol-Endoglin [38] were first cloned into the shuttle vector pShuttle-CMV vector [37]. Therefore, the vector pcDNA3.1-FL-Endoglin was digested with restriction sites Kpn I (Roche, Mannheim, Germany) and Pme I (New England Biolabs GmbH, Frankfurt am Main, Germany) and the resulting fragment cloned into vector pShuttle-CMV cut with Kpn I and EcoR V (Roche).…”

Section: Methodsmentioning

confidence: 99%

Endoglin Trafficking/Exosomal Targeting in Liver Cells Depends on N-Glycosylation

Meurer

Wimmer

Leur

et al. 2019

Cells

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Injury of the liver involves a wound healing partial reaction governed by hepatic stellate cells and portal fibroblasts. Individual members of the transforming growth factor-β (TGF-β) superfamily including TGF-β itself and bone morphogenetic proteins (BMP) exert diverse and partially opposing effects on pro-fibrogenic responses. Signaling by these ligands is mediated through binding to membrane integral receptors type I/type II. Binding and the outcome of signaling is critically modulated by Endoglin (Eng), a type III co-receptor. In order to learn more about trafficking of Eng in liver cells, we investigated the membranal subdomain localization of full-length (FL)-Eng. We could show that FL-Eng is enriched in Caveolin-1-containing sucrose gradient fractions. Since lipid rafts contribute to the pool of exosomes, we could consequently demonstrate for the first time that exosomes isolated from cultured primary hepatic stellate cells and its derivatives contain Eng. Moreover, via adenoviral overexpression, we demonstrate that all liver cells have the capacity to direct Eng to exosomes, irrespectively whether they express endogenous Eng or not. Finally, we demonstrate that block of N-glycosylation does not interfere with dimerization of the receptor, but abrogates the secretion of soluble Eng (sol-Eng) and prevents exosomal targeting of FL-Eng.

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