Transcription Factor TCF3 Promotes Macrophage-Mediated Inflammation and MMP Secretion in Abdominal Aortic Aneurysm by Regulating miR-143-5p/CCL20
Yuejin Li, Rougang Li, Yu Li, Guosan Li, Yiman Zhao, Houyu Mou, Yi Chen, Le Xiao, Kunmei Gong
Abstract
ABSTRACT: Damage to the abdominal aortic wall and the local inflammatory response are key factors resulting in abdominal aortic aneurysm (AAA) formation. During this process, macrophage polarization plays a key role. However, in AAA, the regulatory mechanism of macrophages is still unclear, and further research is needed. In this study, we found that the transcription factor TCF3 was expressed at low levels in AAA. We overexpressed TCF3 and found that TCF3 could inhibit MMP and inflammatory factor expression and promote M2 macrophage polarization, thereby inhibiting the progression of AAA. Knocking down TCF3 could promote M1 polarization and MMP and inflammatory factor expression. In addition, we found that TCF3 increased miR-143-5p expression through transcriptional activation of miR-143-5p , which further inhibited expression of the downstream chemokine CCL20 and promoted M2 macrophage polarization. Our research indicates that TCF3-mediated macrophage polarization plays a key regulatory role in AAA, complementing the role and mechanism of macrophages in the occurrence and development of AAA and providing a scientific basis for AAA treatment.