| First Author | Yuan JN | Year | 2021 |
| Journal | Front Cell Dev Biol | Volume | 9 |
| Pages | 682574 | PubMed ID | 34409030 |
| Mgi Jnum | J:325218 | Mgi Id | MGI:6762240 |
| Doi | 10.3389/fcell.2021.682574 | Citation | Yuan JN, et al. (2021) MiR-302a Limits Vascular Inflammation by Suppressing Nuclear Factor-kappa B Pathway in Endothelial Cells. Front Cell Dev Biol 9:682574 |
| abstractText | The inflammatory response of endothelial cells accelerates various vascular diseases. MicroRNAs (miRNAs) participate in diverse cellular processes during inflammation. In the present study, we found that miR-302a is an effective suppressor of vascular inflammation in endothelial cells. It was revealed that miR-302a exhibited a lower level in a lipopolysaccharide (LPS)-induced mouse model and in patients with vascular inflammatory disease. Genetic haploinsufficiency of miR-302 aggravated the LPS-induced vascular inflammatory response in mice, and overexpression of miR-302a attenuated vascular inflammation in mice. Furthermore, overexpression of miR-302a inhibited the synthesis and secretion of adhesion factors in endothelial cells, and suppressed the adhesion of monocytes to endothelium. In the study of molecular mechanism, we found that miR-302a relieved vascular inflammation mainly by regulating the nuclear factor kappa-B (NF-kappaB) pathway in endothelial cells. The results showed that interleukin-1 receptor-associated kinase4 (IRAK4) and zinc finger protein 91 (ZFP91) were the binding targets of miR-302a. MiR-302a prevented the nuclear translocation of NF-kappaB by inhibiting phosphorylation of IkappaB kinase complex beta (IKKbeta) and inhibitors of kappaBalpha (IkappaBalpha) via targeting IRAK4. In addition, miR-302a downregulated the expression of NF-kappaB by directly binding with ZFP91. These findings indicate that miR-302a negatively regulates inflammatory responses in the endothelium via the NF-kappaB pathway and it may be a novel target for relieving vascular inflammation. |
