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| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Le Ribeuz, Hélène Courboulin, Audrey Ghigna, Maria-Rosa Lambert, Mélanie Hautefort, Aurélie Humbert, Marc Montani, David Cohen-Kaminsky, Sylvia Perros, Frédéric Antigny, Fabrice |
| Abstract | Background The pathogenesis of pulmonary arterial hypertension (PAH) involves many signalling pathways. MicroRNAs are potential candidates involved in simultaneously coordinating multiple genes under such multifactorial conditions. Methods and results MiR-138-5p is overexpressed in pulmonary arterial smooth muscle cells (PASMCs) from PAH patients and in lungs from rats with monocrotaline-induced pulmonary hypertension (MCT-PH). MiR-138-5p is predicted to regulate the expression of the potassium channel KCNK3, whose loss is associated with the development and progression of PAH. We hypothesized that, in vivo, miR-138-5p inhibition would restore KCNK3 lung expression and subsequently alleviate PAH. Nebulization-based delivery of anti-miR-138-5p to rats with established MCT-PH significantly reduced the right ventricular systolic pressure and significantly improved the pulmonary arterial acceleration time (PAAT). These haemodynamic improvements were related to decrease pulmonary vascular remodelling, lung inflammation and pulmonary vascular cell proliferation in situ. In vivo inhibition of miR-138-5p restored KCNK3 mRNA expression and SLC45A3 protein expression in the lungs. Conclusions We confirmed that in vivo inhibition of miR-138-5p reduces the development of PH in experimental MCT-PH. The possible curative mechanisms involve at least the normalization of lung KCNK3 as well as SLC45A3 expression. |
| Related Links | https://respiratory-research.biomedcentral.com/counter/pdf/10.1186/s12931-020-01444-7.pdf |
| Ending Page | 14 |
| Page Count | 14 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| DOI | 10.1186/s12931-020-01444-7 |
| Journal | Respiratory Research |
| Issue Number | 1 |
| Volume Number | 21 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2020-07-16 |
| Access Restriction | Open |
| Subject Keyword | Pneumology Respiratory System miR-138 PAH KCNK3 Proliferation SLC45A3 Pneumology/Respiratory System |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pulmonary and Respiratory Medicine |
| Journal Impact Factor | 4.7/2023 |
| 5-Year Journal Impact Factor | 5.3/2023 |
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