| First Author | Zhang R | Year | 2019 |
| Journal | Am J Physiol Lung Cell Mol Physiol | Volume | 316 |
| Issue | 3 | Pages | L547-L557 |
| PubMed ID | 30628484 | Mgi Jnum | J:310958 |
| Mgi Id | MGI:6762455 | Doi | 10.1152/ajplung.00387.2018 |
| Citation | Zhang R, et al. (2019) MiRNA let-7b promotes the development of hypoxic pulmonary hypertension by targeting ACE2. Am J Physiol Lung Cell Mol Physiol 316(3):L547-L557 |
| abstractText | Angiotensin-converting enzyme 2 (ACE2) protects against hypoxic pulmonary hypertension (HPH) by inhibiting the proliferation and migration of pulmonary artery smooth muscle cells (PASMCs). Under hypoxia, the hypoxia-inducible factor 1alpha (HIF-1alpha) inhibits ACE2 indirectly; however, the underlying mechanism is unclear. In the present study, we found that exposure to chronic hypoxia stimulated microRNA (miRNA) let-7b expression in rat lung via a HIF-1alpha-dependent pathway. Let-7b downregulated ACE2 expression by directly targeting the coding sequence of ACE2. Our in vitro and in vivo results revealed that let-7b contributed to the pathogenesis of HPH by inducing PASMCs proliferation and migration. Let-7b knockout mitigated right ventricle hypertrophy and pulmonary vessel remodeling in HPH by restoring ACE2 expression. Overall, we demonstrated that HIF-1alpha inhibited ACE2 expression via the HIF-1alpha-let-7b-ACE2 axis, which contributed to the pathogenesis of HPH by stimulating PASMCs proliferation and migration. Since let-7b knockout alleviated the development of HPH, let-7b may serve as a potential clinical target for the treatment of HPH. |
