针对ATF6和SNAI1之间的自我放大循环,以抑制纤维化病变中的上皮细胞 - 介质细胞过渡
Tong Wu1, Yan Liu1, Jiyuan Ma1,2
1Department of Ophthalmology, Xijing Hospital, Eye Institute of Chinese PLA, Fourth Military Medical University, 710032 Xi'an, China.
Theranostics
|August 27, 2025
概括
一个涉及激活转录因子6 (ATF6) 和牛家族转录抑制剂1 (SNAI1) 的新型自我放大反循环驱动了未折叠的蛋白质反应依赖的上皮质-介质细胞转换 (EMT). 黑素有效抑制了ATF6-SNAI1循环,为纤维化疾病提供了治疗策略.
科学领域:
- 细胞生物学
- 分子生物学
- 病理学
背景情况:
- 在器官纤维化和瘤中,上皮介质转换 (EMT) 是至关重要的,但其触发分子机制仍然不完全理解.
- 在EMT中涉及到未折叠的蛋白质反应 (UPR),但涉及到的具体途径需要进一步阐明.
研究的目的:
- 确定和描述驱动UPR依赖的EMT的分子机制.
- 研究激活转录因子6 (ATF6) 和牛家族转录抑制剂1 (SNAI1) 在新型自我放大反循环中的作用.
- 评估黑素 (MLT) 在抑制UPR依赖的EMT中的治疗潜力.
主要方法:
- 使用了体内和体外模型,包括小鼠损伤模型和人体透镜扩展剂.
- 进行RNA测序以分析依赖于UPR的EMT机制.
- 使用双露西法酶测定验证了ATF6- SNAI1相互作用,并评估了MLT的抑制作用.
主要成果:
- 在纤维性白内障中,ATF6的高调,其过度表达引起了类似EMT的变化.
- 在ATF6和SNAI1之间发现了一种自我放大的反循环,推动了UPR依赖的EMT进展.
- 黑素有效抑制了依赖于UPR的EMT,并改善了与Atf6结合的EMT变化.
结论:
- ATF6-SNAI1自放大循环是EMT的一个关键介质.
- 用黑激素准这一循环是抑制纤维状况,特别是透镜纤维化的有希望的治疗策略.
更多相关视频
06:02Development of an In Vitro Assay to Evaluate Contractile Function of Mesenchymal Cells that Underwent Epithelial-Mesenchymal Transition
Published on: June 10, 2016
12.3K
06:54Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
13.3K
相关概念视频
01:16TGF - β Signaling Pathway
7.6K
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...
7.6K
01:20The JAK-STAT Signaling Pathway
9.2K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
9.2K
01:24Regulation of Angiogenesis and Blood Supply
2.7K
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...
2.7K
01:22PI3K/mTOR/AKT Signaling Pathway
3.9K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
3.9K