TGF-β1触发的BMI1和SMAD2共同调节miR-191以调节骨形成
Xiao-Fei Zhang1, Zi-Xuan Wang2, Bo-Wen Zhang2
1Center for Translational Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430000, China.
Molecular therapy. Nucleic acids
|March 29, 2024
概括
在骨形成过程中,microRNA-191 (miR-191) 通过转化生长因子β1 (TGF-β1) 进行下调. 抑制miR-191可以增强骨的修复,这表明骨再生的治疗潜力.
科学领域:
- 生物化学 生化学
- 细胞生物学 细胞生物学
- 再生医学是一种再生医学.
背景情况:
- 转化生长因子β1 (TGF-β1) 对于骨质稳定至关重要,但其在骨形成中的信号传递尚未完全理解.
- 微RNAs (miRNAs) 在细胞过程中发挥调节作用,包括骨质生成.
研究的目的:
- 阐明微RNA-191 (miR-191) 在TGF-β1介导的骨形成和再生中的作用.
- 通过TGF-β1信号传递来调节miR-191的分子机制.
主要方法:
- 在骨髓介质干细胞 (BMSCs) 骨质生成过程中量化miR-191水平.
- 分析不同年龄组的骨组织中的miR-191表达.
- 在活体研究中,使用具有miR-191-低BMSC的水凝进行骨修复评估.
- 涉及转录因子BMI1和SMAD2及其与miR-191促进体相互作用的机制研究.
主要成果:
- 在骨质生成过程中,miR-191被下调,并在BMSC中被TGF-β1进一步降低.
- 与中年人相比,儿童的骨组织中观察到较低的miR-191水平,并且与原蛋白I型α1链 (COL1A1) 有负相关.
- 削减miR-191显著增强骨质生成和骨形成in vivo,miR-191低BMSC的水凝显示出强大的骨修复.
- TGF-β1提高了BMI1和pSMAD2的调节;SMAD2激活了miR-191的转录,而BMI1与SMAD2在促进器区域竞争,降低了miR-191水平.
结论:
- TGF-β1诱导的BMI1和SMAD2负面调节miR-191,反过来调节骨形成和再生.
- 抑制miR-191是一个潜在的治疗策略,可以在临床环境中增强骨修复.
关键词:
MT:非编码RNAs的使用.这就是SMAD2的原因.骨损伤和骨的修复骨髓衍生中酶体干细胞 骨髓衍生中酶体干细胞微型RNA-191 是一个骨质发生过程 (osteogenesis)聚组蛋白BMI1BMI1BMI1BMI1BMI1BMI1BMI1BMI1BMI1BMI1BMI1BMI1BMI1BMI1BMI1BMI1BMI1BMI1BMI1BMI1BMI1BMI1BMI1BMI1BMI1BMI1BMI1BMI1BMI2BMI1BMI2BMI2BMI1BMI2BMI2BMI2BMI2BMI2转录规则 转录规则 转录规则转化生长因子β1的转化生长因子β1更多相关视频
11:38Visualization and Quantification of TGFβ/BMP/SMAD Signaling under Different Fluid Shear Stress Conditions using Proximity-Ligation-Assay
Published on: September 14, 2021
3.4K
07:49Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling
Published on: August 3, 2018
11.3K
相关概念视频
01:16TGF - β Signaling Pathway
7.3K
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...
7.3K
01:17Hormones and Bone Tissue
2.7K
The endocrine system produces and secretes hormones, which interact with the skeletal system. These hormones control bone growth, maintain bone once it is formed, and remodel it.
Hormones That Influence Osteoblasts and/or Maintain the Matrix
Several hormones are necessary for controlling bone growth and maintaining the bone matrix. The pituitary gland secretes growth hormone (GH), which, as its name implies, controls bone growth. This happens in several ways: first, it triggers chondrocyte...
Hormones That Influence Osteoblasts and/or Maintain the Matrix
Several hormones are necessary for controlling bone growth and maintaining the bone matrix. The pituitary gland secretes growth hormone (GH), which, as its name implies, controls bone growth. This happens in several ways: first, it triggers chondrocyte...
2.7K
02:23Master 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