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MED12 调节平滑肌细胞功能并参与主动脉夹层的发生。

MED12 Regulates Smooth Muscle Cell Functions and Participates in the Development of Aortic Dissection.

机构信息

Heart Center, Qingdao Women and Children's Hospital, Qingdao University, Qingdao 266034, China.

Key Laboratory of Molecular Biophysics of the Ministry of Education, Center for Human Genome Research, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China.

出版信息

Genes (Basel). 2022 Apr 14;13(4):692. doi: 10.3390/genes13040692.

DOI:10.3390/genes13040692
PMID:35456498
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9027749/
Abstract

Aortic dissection (AD) is a life-threatening disease with high morbidity and mortality, and effective pharmacotherapeutic remedies for it are lacking. Therefore, AD's molecular pathogenesis and etiology must be elucidated. The aim of this study was to investigate the possible mechanism of mediator complex subunit 12 (human: , mouse: )involvement in AD. Firstly, we examined the expression of MED12 protein (human: MED12, mouse: Med12) in the aortic tissues of AD patients and AD mice. Subsequently, gene silencing was accomplished with RNA interference (siRNA). The effects of Med12 on AD and the possible biological mechanisms were investigated based on the proliferation, senescence, phenotypic transformation, and its involved signal pathway of mouse aortic smooth muscle cells (MOVAS), s. The results show that the expression of MED12 in the aortae of AD patients and AD mice was decreased. Moreover, the downregulation of Med12 inhibited the proliferation of MOVAS and promoted senescence. Further research found that Med12, as an inhibitor of the TGFβ1 signaling pathway, reduced the expression of Med12 and enhanced the activity of the TGFβ1 nonclassical signaling pathway, while TGFβ1 inhibited the phenotype transformation and proliferation of MOVAS by inhibiting Med12 synthesis. In conclusion, Med12 affected the phenotype, proliferation, and senescence of MOVAS through the TGFβ signaling pathway. This study provides a potential new target for the prevention and treatment of AD.

摘要

主动脉夹层（AD）是一种致命的疾病，发病率和死亡率都很高，目前缺乏有效的药物治疗方法。因此，必须阐明 AD 的分子发病机制和病因。本研究旨在探讨中介复合物亚基 12（人：，鼠：）在 AD 中的可能作用机制。首先，我们检测了 AD 患者和 AD 小鼠主动脉组织中 MED12 蛋白（人：MED12，鼠：Med12）的表达。随后，采用 RNA 干扰（siRNA）实现基因沉默。基于小鼠主动脉平滑肌细胞（MOVAS）的增殖、衰老、表型转化及其涉及的信号通路，研究了 Med12 对 AD 的影响及其可能的生物学机制。结果表明，AD 患者和 AD 小鼠主动脉中 MED12 的表达降低。此外，下调 Med12 抑制 MOVAS 的增殖并促进衰老。进一步的研究发现，作为 TGFβ1 信号通路的抑制剂，Med12 降低了 Med12 的表达并增强了 TGFβ1 非经典信号通路的活性，而 TGFβ1 通过抑制 Med12 的合成抑制 MOVAS 的表型转化和增殖。总之，Med12 通过 TGFβ 信号通路影响 MOVAS 的表型、增殖和衰老。本研究为 AD 的预防和治疗提供了一个潜在的新靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a6d/9027749/c4d54674abfd/genes-13-00692-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a6d/9027749/b32ac8d72199/genes-13-00692-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a6d/9027749/4c68d2847e3b/genes-13-00692-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a6d/9027749/b737a3ecbff3/genes-13-00692-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a6d/9027749/14e32420ac15/genes-13-00692-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a6d/9027749/c4d54674abfd/genes-13-00692-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a6d/9027749/b32ac8d72199/genes-13-00692-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a6d/9027749/4c68d2847e3b/genes-13-00692-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a6d/9027749/b737a3ecbff3/genes-13-00692-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a6d/9027749/14e32420ac15/genes-13-00692-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a6d/9027749/c4d54674abfd/genes-13-00692-g005.jpg

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