dc.contributor.author | Yang, Dafeng | |
dc.contributor.author | Haemmig, Stefan | |
dc.contributor.author | Zhou, Haoyang | |
dc.contributor.author | Pérez-Cremades, Daniel | |
dc.contributor.author | Sun, Xinghui | |
dc.contributor.author | Chen, Lei | |
dc.contributor.author | Li, Jie | |
dc.contributor.author | Haneo-Mejia, Jorge | |
dc.contributor.author | Yang, Tianlun | |
dc.contributor.author | Hollan, Ivana | |
dc.contributor.author | Feinberg, Mark W. | |
dc.date.accessioned | 2023-01-16T09:55:10Z | |
dc.date.available | 2023-01-16T09:55:10Z | |
dc.date.created | 2021-11-26T09:32:54Z | |
dc.date.issued | 2021 | |
dc.identifier.citation | eLIFE. 2021, 10 1-19. | en_US |
dc.identifier.issn | 2050-084X | |
dc.identifier.uri | https://hdl.handle.net/11250/3043617 | |
dc.description.abstract | Endothelial cell (EC) activation is an early hallmark in the pathogenesis of chronic vascular diseases. MicroRNA-181b (Mir181b) is an important anti-inflammatory mediator in the vascular endothelium affecting endotoxemia, atherosclerosis, and insulin resistance. Herein, we identify that the drug methotrexate (MTX) and its downstream metabolite adenosine exert anti-inflammatory effects in the vascular endothelium by targeting and activating Mir181b expression. Both systemic and endothelial-specific Mir181a2b2-deficient mice develop vascular inflammation, white adipose tissue (WAT) inflammation, and insulin resistance in a diet-induced obesity model. Moreover, MTX attenuated diet-induced WAT inflammation, insulin resistance, and EC activation in a Mir181a2b2-dependent manner. Mechanistically, MTX attenuated cytokine-induced EC activation through a unique adenosine-adenosine receptor A3-SMAD3/4-Mir181b signaling cascade. These findings establish an essential role of endothelial Mir181b in controlling vascular inflammation and that restoring Mir181b in ECs by high-dose MTX or adenosine signaling may provide a potential therapeutic opportunity for anti-inflammatory therapy. | en_US |
dc.language.iso | eng | en_US |
dc.publisher | eLife Sciences Publications | en_US |
dc.rights | Navngivelse 4.0 Internasjonal | * |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/deed.no | * |
dc.title | Methotrexate attenuates vascular inflammation through an adenosine- microRNA-dependent pathway | en_US |
dc.title.alternative | Methotrexate attenuates vascular inflammation through an adenosine- microRNA-dependent pathway | en_US |
dc.type | Peer reviewed | en_US |
dc.type | Journal article | en_US |
dc.description.version | publishedVersion | en_US |
dc.source.pagenumber | 1-19 | en_US |
dc.source.volume | 10 | en_US |
dc.source.journal | eLIFE | en_US |
dc.identifier.doi | 10.7554/eLife.58064 | |
dc.identifier.cristin | 1959531 | |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.qualitycode | 2 | |