Matches in SemOpenAlex for { <https://semopenalex.org/work/W4321787862> ?p ?o ?g. }
- W4321787862 endingPage "4475" @default.
- W4321787862 startingPage "4475" @default.
- W4321787862 abstract "Endothelin-1 (ET-1) has been implicated in the pathogenesis of cardiac fibrosis. Stimulation of endothelin receptors (ETR) with ET-1 leads to fibroblast activation and myofibroblast differentiation, which is mainly characterized by an overexpression of α-smooth muscle actin (α-SMA) and collagens. Although ET-1 is a potent profibrotic mediator, the signal transductions and subtype specificity of ETR contributing to cell proliferation, as well as α-SMA and collagen I synthesis in human cardiac fibroblasts are not well clarified. This study aimed to evaluate the subtype specificity and signal transduction of ETR on fibroblast activation and myofibroblast differentiation. Treatment with ET-1 induced fibroblast proliferation, and synthesis of myofibroblast markers, α-SMA, and collagen I through the ETAR subtype. Inhibition of Gαq protein, not Gαi or Gβγ, inhibited these effects of ET-1, indicating the essential role of Gαq protein-mediated ETAR signaling. In addition, ERK1/2 was required for ETAR/Gαq axis-induced proliferative capacity and overexpression of these myofibroblast markers. Antagonism of ETR with ETR antagonists (ERAs), ambrisentan and bosentan, inhibited ET-1-induced cell proliferation and synthesis of α-SMA and collagen I. Furthermore, ambrisentan and bosentan promoted the reversal of myofibroblasts after day 3 of treatment, with loss of proliferative ability and a reduction in α-SMA synthesis, confirming the restorative effects of ERAs. This novel work reports on the ETAR/Gαq/ERK signaling pathway for ET-1 actions and blockade of ETR signaling with ERAs, representing a promising therapeutic strategy for prevention and restoration of ET-1-induced cardiac fibrosis." @default.
- W4321787862 created "2023-02-25" @default.
- W4321787862 creator A5001713646 @default.
- W4321787862 creator A5003082556 @default.
- W4321787862 creator A5006468349 @default.
- W4321787862 creator A5041976945 @default.
- W4321787862 date "2023-02-24" @default.
- W4321787862 modified "2023-10-14" @default.
- W4321787862 title "Endothelin-1 Induces Cell Proliferation and Myofibroblast Differentiation through the ETAR/Gαq/ERK Signaling Pathway in Human Cardiac Fibroblasts" @default.
- W4321787862 cites W1765265525 @default.
- W4321787862 cites W18385981 @default.
- W4321787862 cites W1964896698 @default.
- W4321787862 cites W1970102552 @default.
- W4321787862 cites W1970235514 @default.
- W4321787862 cites W1975484377 @default.
- W4321787862 cites W1978158142 @default.
- W4321787862 cites W1978401329 @default.
- W4321787862 cites W1979632514 @default.
- W4321787862 cites W1981269760 @default.
- W4321787862 cites W1981493299 @default.
- W4321787862 cites W2005422348 @default.
- W4321787862 cites W2007750689 @default.
- W4321787862 cites W2015582757 @default.
- W4321787862 cites W2025252445 @default.
- W4321787862 cites W2040420658 @default.
- W4321787862 cites W2040441659 @default.
- W4321787862 cites W2043199191 @default.
- W4321787862 cites W2050153745 @default.
- W4321787862 cites W2050863125 @default.
- W4321787862 cites W2052017836 @default.
- W4321787862 cites W2055848305 @default.
- W4321787862 cites W2061869453 @default.
- W4321787862 cites W2070545304 @default.
- W4321787862 cites W2072055719 @default.
- W4321787862 cites W2079025387 @default.
- W4321787862 cites W2083834362 @default.
- W4321787862 cites W2083980460 @default.
- W4321787862 cites W2086670943 @default.
- W4321787862 cites W2100575239 @default.
- W4321787862 cites W2104825830 @default.
- W4321787862 cites W2107277218 @default.
- W4321787862 cites W2115751707 @default.
- W4321787862 cites W2117720582 @default.
- W4321787862 cites W2127088794 @default.
- W4321787862 cites W2134734822 @default.
- W4321787862 cites W2148795098 @default.
- W4321787862 cites W2162820159 @default.
- W4321787862 cites W2163498169 @default.
- W4321787862 cites W2166811364 @default.
- W4321787862 cites W2192080449 @default.
- W4321787862 cites W2332545497 @default.
- W4321787862 cites W2518476176 @default.
- W4321787862 cites W2583626617 @default.
- W4321787862 cites W2607257758 @default.
- W4321787862 cites W2733723804 @default.
- W4321787862 cites W2783034150 @default.
- W4321787862 cites W2809779343 @default.
- W4321787862 cites W2887191177 @default.
- W4321787862 cites W2912654919 @default.
- W4321787862 cites W2943324738 @default.
- W4321787862 cites W2968976791 @default.
- W4321787862 cites W3009157119 @default.
- W4321787862 cites W3196202660 @default.
- W4321787862 cites W4210343616 @default.
- W4321787862 cites W4287448496 @default.
- W4321787862 cites W4308712367 @default.
- W4321787862 cites W4308786696 @default.
- W4321787862 doi "https://doi.org/10.3390/ijms24054475" @default.
- W4321787862 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36901906" @default.
- W4321787862 hasPublicationYear "2023" @default.
- W4321787862 type Work @default.
- W4321787862 citedByCount "4" @default.
- W4321787862 countsByYear W43217878622023 @default.
- W4321787862 crossrefType "journal-article" @default.
- W4321787862 hasAuthorship W4321787862A5001713646 @default.
- W4321787862 hasAuthorship W4321787862A5003082556 @default.
- W4321787862 hasAuthorship W4321787862A5006468349 @default.
- W4321787862 hasAuthorship W4321787862A5041976945 @default.
- W4321787862 hasBestOaLocation W43217878621 @default.
- W4321787862 hasConcept C126322002 @default.
- W4321787862 hasConcept C144980905 @default.
- W4321787862 hasConcept C149601957 @default.
- W4321787862 hasConcept C170493617 @default.
- W4321787862 hasConcept C185592680 @default.
- W4321787862 hasConcept C189165786 @default.
- W4321787862 hasConcept C207865475 @default.
- W4321787862 hasConcept C2777420927 @default.
- W4321787862 hasConcept C2780381497 @default.
- W4321787862 hasConcept C2780559512 @default.
- W4321787862 hasConcept C2781109936 @default.
- W4321787862 hasConcept C502942594 @default.
- W4321787862 hasConcept C54355233 @default.
- W4321787862 hasConcept C55493867 @default.
- W4321787862 hasConcept C62112901 @default.
- W4321787862 hasConcept C62478195 @default.
- W4321787862 hasConcept C71924100 @default.
- W4321787862 hasConcept C81885089 @default.
- W4321787862 hasConcept C86492073 @default.