Abstract:
:Endothelial-mesenchymal transition (EndMT) is a frequent event in endothelial dysfunction, which is associated with pulmonary arterial hypertension (PAH). MiR-181 family members exert diverse effects in multiple biological processes. However, the relationships between miR-181b-5p (miR-181b) and EndMT in PAH are not well understood. In this study, Sprague-Dawley (SD) rats were injected with monocrotaline (MCT) to establish PAH model, and primary rat pulmonary arterial endothelial cells (rPAECs) were treated with TNF-α, TGFβ1 and IL-1β in combination to induce EndMT (I-EndMT). Then we explored miR-181b expression and examined its functional role in PAH. Our data showed that miR-181b was down-expressed in PAH, and its overexpression attenuated the hemodynamics, pulmonary vascular hypertrophy, right ventricular remodeling and EndMT process in MCT-induced PAH rats. In I-EndMT rPAECs, we observed that inducing miR-181b reversed the decrease of endothelial markers and increase of mesenchymal markers. However, knockdown of miR-181b induced similar effects to EndMT. In addition, endocan and TGFBR1 levels were also increased in EndMT, which were negatively regulated by miR-181b. Luciferase activity results indicated that endocan and TGFBR1 were direct target genes of miR-181b. In summary, our findings firstly demonstrate that the beneficial effect of miR-181b on PAH may be associated with endocan/TGFBR1-mediated EndMT, providing a new insight into the diagnosis and treatment of PAH.
journal_name
Toxicol Appl Pharmacoljournal_title
Toxicology and applied pharmacologyauthors
Zhao H,Wang Y,Zhang X,Guo Y,Wang Xdoi
10.1016/j.taap.2019.114827subject
Has Abstractpub_date
2020-01-01 00:00:00pages
114827eissn
0041-008Xissn
1096-0333pii
S0041-008X(19)30435-1journal_volume
386pub_type
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