Article ; Online: MicroRNA-31 regulates TNF-α and IL-17A co-induced-endothelial cell apoptosis by repressing E2F6.
Biochemical and biophysical research communications
2023 Volume 666, Page(s) 76–82
Abstract: Vascular endothelial cell (VEC) apoptosis is the fundamental cause of pulmonary arterial hypertension. MicroRNA-31 (MiR-31) is a novel target for hypertension treatment. However, the role and mechanism of miR-31 in the apoptosis of VECs remain unclear. ... ...
| Abstract | Vascular endothelial cell (VEC) apoptosis is the fundamental cause of pulmonary arterial hypertension. MicroRNA-31 (MiR-31) is a novel target for hypertension treatment. However, the role and mechanism of miR-31 in the apoptosis of VECs remain unclear. The purpose of this study is to determine whether miR-31 plays an important role in VEC apoptosis as well as the detailed mechanisms involved. We found that pro-inflammatory cytokines IL-17A and TNF-α were highly expressed in serum and aorta, and the expression of miR-31 was significantly increased in aortic intimal tissue from Angiotensin II (AngII)- induced hypertensive mice (WT-AngII) compared with control mice (WT-NC). In vitro, co-stimulation of VECs with IL-17A and TNF-α resulted in increased expression of miR-31 and VEC apoptosis. MiR-31 inhibition strikingly decreased TNF-α and IL-17A co-induced VEC apoptosis. Mechanistically, in IL-17A and TNF-α co-stimulated VECs (co-induced VECs), we found that the activation of the NF-κB signal effectively increased the expression of miR-31. Dual-luciferase reporter gene assay revealed that miR-31 directly targeted and inhibited the expression of the E2F transcription factor 6 (E2F6). The expression of E2F6 was decreased in Co-induced VECs. MiR-31 inhibition significantly alleviated the decreased expression of E2F6 in co-induced VECs. Consistent with the co-stimulated effect of IL-17A and TNF-α on VECs, transfection of siRNA E2F6 induced cell apoptosis without the stimulation of the above cytokines. In conclusion, TNF-α and IL-17A generated in the aortic vascular tissue and serum from Ang II-induced hypertensive mice could trigger VECs apoptosis by the miR-31/E2F6 axis. To sum up, our study suggests that the key factor between cytokine co-stimulation effect and VEC apoptosis was miR-31/E2F6 axis, which was mainly regulated by NF-қB signaling pathway. This gives us a new sight to treat hypertension-associated VR. |
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| MeSH term(s) | Animals ; Mice ; Apoptosis ; Cytokines/metabolism ; Endothelial Cells/metabolism ; Hypertension/metabolism ; Interleukin-17/pharmacology ; Interleukin-17/metabolism ; MicroRNAs/metabolism ; NF-kappa B/metabolism ; Tumor Necrosis Factor-alpha/metabolism |
| Chemical Substances | Cytokines ; Interleukin-17 ; MicroRNAs ; NF-kappa B ; Tumor Necrosis Factor-alpha ; Il17a protein, mouse ; E2f6 protein, mouse ; Mirn31 microRNA, mouse ; Tnf protein, mouse |
| Language | English |
| Publishing date | 2023-05-03 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 205723-2 |
| ISSN | 1090-2104 ; 0006-291X ; 0006-291X |
| ISSN (online) | 1090-2104 ; 0006-291X |
| ISSN | 0006-291X |
| DOI | 10.1016/j.bbrc.2023.05.012 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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