microRNA-637/661 ameliorate hypoxic-induced pulmonary arterial hypertension by targeting TRIM29 signaling pathway
Abstract The pathogenesis of pulmonary arterial hypertension (PAH) is closely linked to the abnormal proliferation of pulmonary artery smooth muscle cells. Studies have demonstrated that microRNAs play pivotal roles in the progression of pulmonary hypertension. We found that microRNA-637 (miR-637) a...
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Nature Portfolio
2024-11-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-024-79769-2 |
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| author | Liyang Jiang Weiyi Tao Jun Liu Aixiang Yang Jie Zhou |
| author_facet | Liyang Jiang Weiyi Tao Jun Liu Aixiang Yang Jie Zhou |
| author_sort | Liyang Jiang |
| collection | DOAJ |
| description | Abstract The pathogenesis of pulmonary arterial hypertension (PAH) is closely linked to the abnormal proliferation of pulmonary artery smooth muscle cells. Studies have demonstrated that microRNAs play pivotal roles in the progression of pulmonary hypertension. We found that microRNA-637 (miR-637) and microRNA-661 (miR-661) are expressed at low levels in the serum of PAH patients. Moreover, the overexpression of miR-637 or miR-661 inhibited human pulmonary artery smooth muscle cell (HPASMC) proliferation and migration in hypoxic culture. Mechanistically, we overexpressed these two microRNAs in HPASMCs, and the RNA-sequencing (RNA-seq) results demonstrated that TRIM29 mRNA was suppressed, indicating that TRIM29 is a substrate. TRIM29 accumulates in the serum of patients with PAH and promotes cell proliferation and migration by activating AKT/mTOR signalling. In addition, overexpression of miR-637 or miR-661 reversed TRIM29-mediated HPASMC proliferation and migration. This study revealed that miR-637 and miR-661 are able to inhibit the proliferation ability of HPASMCs under hypoxic conditions through targeting TRIM29, suggesting that the microRNA-637/661/TRIM29 axis may act as a target for PAH treatment. |
| format | Article |
| id | doaj-art-e035c6fa01e8448daf7af4ae541303c3 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-e035c6fa01e8448daf7af4ae541303c32024-11-17T12:28:06ZengNature PortfolioScientific Reports2045-23222024-11-0114111010.1038/s41598-024-79769-2microRNA-637/661 ameliorate hypoxic-induced pulmonary arterial hypertension by targeting TRIM29 signaling pathwayLiyang Jiang0Weiyi Tao1Jun Liu2Aixiang Yang3Jie Zhou4Department of Intensive Care Unit, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal HospitalDepartment of Intensive Care Unit, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal HospitalDepartment of Intensive Care Unit, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal HospitalDepartment of Intensive Care Unit, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal HospitalDepartment of Intensive Care Unit, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal HospitalAbstract The pathogenesis of pulmonary arterial hypertension (PAH) is closely linked to the abnormal proliferation of pulmonary artery smooth muscle cells. Studies have demonstrated that microRNAs play pivotal roles in the progression of pulmonary hypertension. We found that microRNA-637 (miR-637) and microRNA-661 (miR-661) are expressed at low levels in the serum of PAH patients. Moreover, the overexpression of miR-637 or miR-661 inhibited human pulmonary artery smooth muscle cell (HPASMC) proliferation and migration in hypoxic culture. Mechanistically, we overexpressed these two microRNAs in HPASMCs, and the RNA-sequencing (RNA-seq) results demonstrated that TRIM29 mRNA was suppressed, indicating that TRIM29 is a substrate. TRIM29 accumulates in the serum of patients with PAH and promotes cell proliferation and migration by activating AKT/mTOR signalling. In addition, overexpression of miR-637 or miR-661 reversed TRIM29-mediated HPASMC proliferation and migration. This study revealed that miR-637 and miR-661 are able to inhibit the proliferation ability of HPASMCs under hypoxic conditions through targeting TRIM29, suggesting that the microRNA-637/661/TRIM29 axis may act as a target for PAH treatment.https://doi.org/10.1038/s41598-024-79769-2Pulmonary arterial hypertensionmicroRNATRIM29RNA-seqAKT/mTOR signalling |
| spellingShingle | Liyang Jiang Weiyi Tao Jun Liu Aixiang Yang Jie Zhou microRNA-637/661 ameliorate hypoxic-induced pulmonary arterial hypertension by targeting TRIM29 signaling pathway Scientific Reports Pulmonary arterial hypertension microRNA TRIM29 RNA-seq AKT/mTOR signalling |
| title | microRNA-637/661 ameliorate hypoxic-induced pulmonary arterial hypertension by targeting TRIM29 signaling pathway |
| title_full | microRNA-637/661 ameliorate hypoxic-induced pulmonary arterial hypertension by targeting TRIM29 signaling pathway |
| title_fullStr | microRNA-637/661 ameliorate hypoxic-induced pulmonary arterial hypertension by targeting TRIM29 signaling pathway |
| title_full_unstemmed | microRNA-637/661 ameliorate hypoxic-induced pulmonary arterial hypertension by targeting TRIM29 signaling pathway |
| title_short | microRNA-637/661 ameliorate hypoxic-induced pulmonary arterial hypertension by targeting TRIM29 signaling pathway |
| title_sort | microrna 637 661 ameliorate hypoxic induced pulmonary arterial hypertension by targeting trim29 signaling pathway |
| topic | Pulmonary arterial hypertension microRNA TRIM29 RNA-seq AKT/mTOR signalling |
| url | https://doi.org/10.1038/s41598-024-79769-2 |
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