In vivo miR-138-5p inhibition alleviates monocrotaline-induced pulmonary hypertension and normalizes pulmonary KCNK3 and SLC45A3 expression
| Autor: | Le Ribeuz, Hélène, Courboulin, Audrey, Ghigna, Maria-Rosa, Lambert, Mélanie, Hautefort, Aurélie, Humbert, Marc, Montani, David, Cohen-Kaminsky, Sylvia, Perros , Frédéric, Antigny, Fabrice |
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| Přispěvatelé: | INSERM UMR_S 999, Hôpital Marie Lannelongue, Le Plessis-Robinson, France |
| Rok vydání: | 2020 |
| Předmět: |
Male
Monosaccharide Transport Proteins SLC45A3 Proliferation miR-138 Nerve Tissue Proteins Pulmonary Artery Vascular Remodeling Potassium Channels Tandem Pore Domain [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system Administration Inhalation Animals Humans Arterial Pressure Rats Wistar Cells Cultured Cell Proliferation lcsh:RC705-779 Pulmonary Arterial Hypertension Monocrotaline Research Antagomirs lcsh:Diseases of the respiratory system PAH Disease Models Animal MicroRNAs Gene Expression Regulation KCNK3 Signal Transduction |
| Zdroj: | Respiratory Research Respiratory Research, BioMed Central, 2020, 21, ⟨10.1186/s12931-020-01444-7⟩ Respiratory Research, Vol 21, Iss 1, Pp 1-14 (2020) |
| ISSN: | 1465-993X 1465-9921 |
| DOI: | 10.1186/s12931-020-01444-7⟩ |
| Popis: | International audience; 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. |
| Databáze: | OpenAIRE |
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