FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3046695108> ?p ?o ?g. }

• W3046695108 endingPage "1137" @default.
• W3046695108 startingPage "1122" @default.
• W3046695108 abstract "Hereditary hemorrhagic telangiectasia (HHT) is a genetic disease caused by mutations in ENG, ALK1, or SMAD4. Since proteins from all 3 HHT genes are components of signal transduction of TGF-β (transforming growth factor β) family members, it has been hypothesized that HHT is a disease caused by defects in the ENG-ALK1-SMAD4 linear signaling. However, in vivo evidence supporting this hypothesis is scarce.We tested this hypothesis and investigated the therapeutic effects and potential risks of induced-ALK1 or -ENG overexpression (OE) for HHT.We generated a novel mouse allele (ROSA26Alk1) in which HA (human influenza hemagglutinin)-tagged ALK1 and bicistronic eGFP expression are induced by Cre activity. We examined whether ALK1-OE using the ROSA26Alk1 allele could suppress the development of arteriovenous malformations (AVMs) in wounded adult skin and developing retinas of Alk1- and Eng-inducible knockout (iKO) mice. We also used a similar approach to investigate whether ENG-OE could rescue AVMs. Biochemical and immunofluorescence analyses confirmed the Cre-dependent OE of the ALK1-HA transgene. We could not detect any pathological signs in ALK1-OE mice up to 3 months after induction. ALK1-OE prevented the development of retinal AVMs and wound-induced skin AVMs in Eng-iKO as well as Alk1-iKO mice. ALK1-OE normalized expression of SMAD and NOTCH target genes in ENG-deficient endothelial cells (ECs) and restored the effect of BMP9 (bone morphogenetic protein 9) on suppression of phosphor-AKT levels in these endothelial cells. On the other hand, ENG-OE could not inhibit the AVM development in Alk1-iKO models.These data support the notion that ENG and ALK1 form a linear signaling pathway for the formation of a proper arteriovenous network during angiogenesis. We suggest that ALK1 OE or activation can be an effective therapeutic strategy for HHT. Further research is required to study whether this therapy could be translated into treatment for humans." @default.
• W3046695108 created "2020-08-07" @default.
• W3046695108 creator A5012967178 @default.
• W3046695108 creator A5025292160 @default.
• W3046695108 creator A5027154926 @default.
• W3046695108 creator A5041078470 @default.
• W3046695108 creator A5041714425 @default.
• W3046695108 creator A5069489177 @default.
• W3046695108 creator A5085177179 @default.
• W3046695108 creator A5091174671 @default.
• W3046695108 date "2020-10-09" @default.
• W3046695108 modified "2023-10-05" @default.
• W3046695108 title "Overexpression of Activin Receptor-Like Kinase 1 in Endothelial Cells Suppresses Development of Arteriovenous Malformations in Mouse Models of Hereditary Hemorrhagic Telangiectasia" @default.
• W3046695108 cites W1538926863 @default.
• W3046695108 cites W156646843 @default.
• W3046695108 cites W1576609386 @default.
• W3046695108 cites W1970826769 @default.
• W3046695108 cites W1973203818 @default.
• W3046695108 cites W1981358858 @default.
• W3046695108 cites W1982130799 @default.
• W3046695108 cites W1982639675 @default.
• W3046695108 cites W1983322974 @default.
• W3046695108 cites W1992224115 @default.
• W3046695108 cites W1994481502 @default.
• W3046695108 cites W1997538895 @default.
• W3046695108 cites W2014415717 @default.
• W3046695108 cites W2015902581 @default.
• W3046695108 cites W2019453487 @default.
• W3046695108 cites W2019832656 @default.
• W3046695108 cites W2021605609 @default.
• W3046695108 cites W2025823855 @default.
• W3046695108 cites W2026066037 @default.
• W3046695108 cites W2027760929 @default.
• W3046695108 cites W2030717725 @default.
• W3046695108 cites W2034761148 @default.
• W3046695108 cites W2035005764 @default.
• W3046695108 cites W2035282407 @default.
• W3046695108 cites W2050332147 @default.
• W3046695108 cites W2052927933 @default.
• W3046695108 cites W2053728895 @default.
• W3046695108 cites W2060372234 @default.
• W3046695108 cites W2066990977 @default.
• W3046695108 cites W2075998623 @default.
• W3046695108 cites W2078717028 @default.
• W3046695108 cites W2090539783 @default.
• W3046695108 cites W2100976582 @default.
• W3046695108 cites W2108668719 @default.
• W3046695108 cites W2109947902 @default.
• W3046695108 cites W2116011829 @default.
• W3046695108 cites W2116414309 @default.
• W3046695108 cites W2121052913 @default.
• W3046695108 cites W2127551299 @default.
• W3046695108 cites W2130139387 @default.
• W3046695108 cites W2131246162 @default.
• W3046695108 cites W2132208081 @default.
• W3046695108 cites W2150249204 @default.
• W3046695108 cites W2156599426 @default.
• W3046695108 cites W2159508011 @default.
• W3046695108 cites W2160489211 @default.
• W3046695108 cites W2163504684 @default.
• W3046695108 cites W2168558463 @default.
• W3046695108 cites W2297776995 @default.
• W3046695108 cites W2416837077 @default.
• W3046695108 cites W2417738140 @default.
• W3046695108 cites W2557883191 @default.
• W3046695108 cites W2597618297 @default.
• W3046695108 cites W2619222934 @default.
• W3046695108 cites W2619574793 @default.
• W3046695108 cites W2619679718 @default.
• W3046695108 cites W2743294871 @default.
• W3046695108 cites W2770216137 @default.
• W3046695108 cites W2773611494 @default.
• W3046695108 cites W2818354613 @default.
• W3046695108 cites W2883833333 @default.
• W3046695108 cites W2889896836 @default.
• W3046695108 cites W2893094148 @default.
• W3046695108 cites W2899792317 @default.
• W3046695108 cites W2911453152 @default.
• W3046695108 cites W2914386434 @default.
• W3046695108 cites W2969763210 @default.
• W3046695108 cites W2980829890 @default.
• W3046695108 cites W4210412627 @default.
• W3046695108 doi "https://doi.org/10.1161/circresaha.119.316267" @default.
• W3046695108 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7554133" @default.
• W3046695108 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/32762495" @default.
• W3046695108 hasPublicationYear "2020" @default.
• W3046695108 type Work @default.
• W3046695108 sameAs 3046695108 @default.
• W3046695108 citedByCount "23" @default.
• W3046695108 countsByYear W30466951082020 @default.
• W3046695108 countsByYear W30466951082021 @default.
• W3046695108 countsByYear W30466951082022 @default.
• W3046695108 countsByYear W30466951082023 @default.
• W3046695108 crossrefType "journal-article" @default.
• W3046695108 hasAuthorship W3046695108A5012967178 @default.
• W3046695108 hasAuthorship W3046695108A5025292160 @default.
• W3046695108 hasAuthorship W3046695108A5027154926 @default.
• W3046695108 hasAuthorship W3046695108A5041078470 @default.

• next