Upregulation of miR-222-3p alleviates the symptom of aortic dissection through targeting STAT3

作者：Tianci Chai, Xiaojie Yang, Xinghui Zhuang, Zhihuang Qiu, Hui Zheng, Meiling Cai, Yunnan Hu, Meifang Chen, Xianbiao Xie, Keyuan Chen, Lingyu Lin, Liangwan Chen · 发表于：Life Sciences · 年份：2022 · DOI：10.1016/j.lfs.2022.121051 · 被引用次数：10 · 研究领域：Aortic Disease and Treatment Approaches、Connective tissue disorders research、MicroRNA in disease regulation

OBJECTIVE: This study sought to investigate the differentially expressed miRNAs in Aortic dissection (AD) and explore the downstream mechanisms in regulating AD. METHODS: Exosomes of AD patients and healthy people were isolated by differential centrifugation, and the differentially expressed miRNAs were evaluated by RNA sequencing. The downstream target of miR-222-3p was predicted by bioinformatics method and validated by dual-luciferase assay. Angiotensin II and Promethazine were used to establish AD mouse model and platelet-derived growth factor BB (PDGF-BB) was used to induce human vascular smooth muscle cells (HVSMCs) to elucidate the effect of miR-222-3p upregulation on AD in vivo and in vitro. The relative level of miR-222-3p was evaluated by RT-qPCR. The level of several proteins was investigated by Western blot. Immunofluorescence staining was used to detect the stress fiber formation. Cell migration was evaluated by wound healing and Transwell assay. The proliferation, cell cycle and apoptosis of HVSMCs were assessed by CCK-8 and flow cytometry, respectively. RESULTS: MiR-222-3p was downregulated in AD and PDGF-BB induced HVSMCs. The upregulation of miR-222-3p alleviated the symptom of AD in vivo by targeting STAT3, and inhibited stress fiber formation, abnormal migration, proliferation and apoptosis of HVSMCs induced by PDGF-BB by regulating the expression of α-SMA, SM22α, MMP2, MMP9 and p-Smad2. CONCLUSION: The upregulation of miR-222-3p attenuates the progression ...