在光滑肌细胞中,TBX18对转录的调节对于正常的大动脉发育和恒温是必不可少的
Debanjan Mukherjee1,2,3,4,5,6, Veronica Larcher1,2,3, Hanna Winter7,8
1Institute of Cardiovascular Regeneration, Goethe University, Frankfurt am Main 60590, Germany.
Cardiovascular research
|November 20, 2025
概括
转录因子TBX18对于正常的大动脉发育至关重要,并防止成年人的不良重塑. 在光滑肌细胞中缺少它会导致大动脉形,并加剧马方综合征的并发症.
科学领域:
- 心血管生物学 心血管生物学
- 发展生物学 发展生物学
- 分子遗传学 分子遗传学
背景情况:
- TBX18是一种转录因子,在心血管和泌尿器官发育中具有已知的作用.
- 它在主动脉中的特定功能以前没有被研究过.
- 大动脉疾病,如动脉瘤,是死亡的重要原因.
研究的目的:
- 调查TBX18在大动脉发育和恒温中的作用.
- 为了确定TBX18是否影响不良改造和动脉瘤形成.
主要方法:
- 野生类型和转基因小鼠在光滑肌细胞 (SMC) 中进行了Tbx18剥离的组织学和定量成像分析.
- 评估胚胎和成年人除表型,包括与马尔法因子突变的结合作用.
- 在小鼠和人类大动脉SMC中进行多组 (转录组,转录组) 和ChIP-seq分析.
- 对患有大动脉动脉瘤的人类患者样本的分析.
主要成果:
- 在胚胎发育期间和成年后,Tbx18在大动脉SMC中表达.
- 胚胎Tbx18切除导致严重的大动脉形和致死性.
- 成年人Tbx18切除加剧了马芬综合征表型,导致大动脉扩张和致死性.
- TBX18直接调节参与大动脉重塑的基因,其表达在人体动脉瘤中被下调.
结论:
- 在SMC中,TBX18对于正常的大动脉发育至关重要.
- TBX18在预防成人大动脉中不适应性基因表达程序方面发挥着至关重要的作用.
- 降低TBX18的调节与动脉瘤的严重程度有关,强调其作为治疗点的潜力.
更多相关视频
10:57Using In Vivo and Tissue and Cell Explant Approaches to Study the Morphogenesis and Pathogenesis of the Embryonic and Perinatal Aorta
Published on: September 12, 2017
8.9K
07:49Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling
Published on: August 3, 2018
11.7K
相关概念视频
02:23Master Transcription Regulators
7.7K
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
7.7K
02:23Master Transcription Regulators
2.7K
2.7K
01:30General Transcription Factors
6.7K
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
6.7K
02:16Transcription Factors
82.2K
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
82.2K
01:16TGF - β Signaling Pathway
10.4K
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
10.4K
01:24Regulation of Angiogenesis and Blood Supply
3.3K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
3.3K