转录因子Sp1的缺陷导致过敏性心肌病变
Fulei Zhang1,2,3, Huixing Zhou1,2,3, Jinfeng Xue4
1State Key Laboratory of Cardiology (F.Z., H.Z., Y.Z., L.Z., J.L., G.F., H.L., Y. Wu, R.D., X.H., Yi Liu, L.L., J.Y., D.L., Y.-H.C.), Shanghai East Hospital, Tongji University School of Medicine, China.
Circulation research
|January 10, 2024
概括
特异性蛋白1 (SP1) 缺乏导致高性心肌病 (HCM). 在小鼠和人类细胞中,SP1过度表达为HCM提供了治疗效益,将SP1确定为潜在的治疗标.
科学领域:
- 心脏病学 心脏病学
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 增高性心肌病变 (HCM) 是一种常见的遗传性心脏病,其非遗传性原因不明.
- 像SP1这样的转录因子与细胞生长和心脏缩有关.
- 研究了SP1在HCM病原发生中的作用.
研究的目的:
- 研究SP1在心脏缩和HCM中的作用.
- 探索SP1作为HCM的潜在治疗点.
主要方法:
- 在SP1小鼠中产生心脏特异性条件淘汰.
- 分析心脏表型使用心声回声学,组织学和电子显微镜.
- 利用RNA测序,ChIP测序,AAV实验和hiPSC-CM来探索SP1的机制和治疗潜力.
主要成果:
- 在小鼠中,SP1缺乏和hiPSC-CMs诱导了类似HCM的表型,包括心肌缩和纤维化.
- TUFT1被确定为一个关键的SP1目标基因;TUFT1过度表达挽救了SP1敲击诱导的缩.
- SP1过度表达改善了小鼠和人类细胞中的HCM表型.
结论:
- SP1 缺乏是 HCM 的原因.
- SP1在维持心脏结构和功能方面发挥着至关重要的作用.
- SP1过度表达证明了HCM治疗的治疗潜力.
相关概念视频
General Transcription Factors
5.3K
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...
5.3K
Transcription Factors
75.9K
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...
75.9K
Pathophysiology of Heart Failure
1.6K
Heart failure (HF) is a progressive syndrome involving ventricles that leads to inadequate cardiac output. It can be classified based on location and output or ejection fraction. Ejection fraction (EF) is an essential measurement in the diagnosis and surveillance of HF. Reduced EF corresponds to systolic heart failure (HFrEF). However, HF with preserved ejection fraction (HFpEF) is becoming increasingly prevalent. Also known as diastolic HF, this form of HF is related to aging. The...
1.6K
Master Transcription Regulators
6.9K
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...
6.9K
Alternative RNA Splicing
21.2K
Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
21.2K
Imbalances in Cardiac Output
1.4K
The heart's primary function is to pump blood throughout the body, maintaining a balance between blood sent out (cardiac output) and blood returning (venous return). If this balance is disrupted, it can result in congestive heart failure (CHF), a severe condition where the heart becomes an inefficient pump, leading to inadequate blood circulation.
CHF can occur due to the failure of either side of the heart. Left-side failure leads to pulmonary congestion—the right side continues to send...
CHF can occur due to the failure of either side of the heart. Left-side failure leads to pulmonary congestion—the right side continues to send...
1.4K


