MED12 Regulates Smooth Muscle Cell Functions and Participates in the Development of Aortic Dissection.
MED12 Regulates Smooth Muscle Cell Functions and Participates in the Development of Aortic Dissection.
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MED12 调节平滑肌细胞功能并参与主动脉夹层的发展
作者：
主动脉夹层（AD）是一种高发病率和高死亡率的危及生命的疾病，目前尚无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。本研究的目的是探讨介质复合物亚基12（人：MED12，小鼠：Med12）参与AD的可能机制。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，小鼠：Med12）的表达。随后，Med12基因沉默与RNA干扰（siRNA）完成。本研究通过对小鼠主动脉平滑肌细胞（MOVAS）增殖、衰老、表型转化及其相关信号通路的研究，探讨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小鼠大脑皮层中MED12的表达均降低。Med12的下调可抑制MOVAS的增殖并促进衰老。进一步研究发现，Med12作为TGFβ1信号通路的抑制剂，可降低Med12的表达，增强TGFβ1非经典信号通路的活性，而TGFβ1则通过抑制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。
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: MED12, mouse: Med12)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, Med12 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.
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影响因子：
39.3
作者：
Detaint, Delphine;Faivre, Laurence;Jondeau, Guillaume
通讯作者：
Jondeau, Guillaume
影响因子：
39.3
作者：
Erbel, Raimund;Aboyans, Victor;Vrints, Christiaan J. M.
通讯作者：
Vrints, Christiaan J. M.
影响因子：
20.1
作者：
Marshall, Lynn M.;Carlson, Eric J.;Sakai, Lynn Y.
通讯作者：
Sakai, Lynn Y.
影响因子：
4.6
作者：
Bogunovic, Natalija;Meekel, Jorn P.;Yeung, Kak K.
通讯作者：
Yeung, Kak K.
DOI：
10.1073/pnas.0709749105
发表时间：
2008-05-06
影响因子：
11.1
作者：
Carrera, Ines;Janody, Florence;Treisman, Jessica E.
通讯作者：
Treisman, Jessica E.