增加FGF10的热稳定性导致在发育过程中产生子宫外信号
Aleksandra A Czyrek1,2,3, Karolina Baran3, Eva Hruba4,5
1Department of Biology, Faculty of Medicine, Masaryk University, Brno, 62500, Czech Republic.
Cellular and molecular life sciences : CMLS
|April 21, 2025
概括
纤维细胞生长因子10 (FGF10) 是热不稳定的,限制其功能. 工程稳定FGF10变种显示增强的肺和四肢发育,表明再生医学的治疗潜力.
科学领域:
- 生物化学 生物化学
- 发展生物学 发展生物学
- 分子生物学分子生物学
背景情况:
- 纤维细胞生长因子 (FGFs) 对发育和组织修复至关重要.
- FGFs的功能调节,特别是通过热力学稳定性,尚不清楚.
- FGF10是肢体和肺部发育的关键形态原体.
研究的目的:
- 调查热力学稳定性在FGF10功能中的作用.
- 设计热稳定的FGF10变体并评估它们的生物活性.
- 探索稳定的FGF10变体在肺和四肢发育和再生中的治疗潜力.
主要方法:
- 使用定向突变发生来产生稳定的FGF10变体 (FGF10-STABs).
- 在体外细胞测试中评估了受体结合,信号激活和基因表达.
- 在体内研究中使用了小鼠肺部扩展剂,胚胎四肢生长试验和四肢芽植入.
- 人类诱导的多能干细胞衍生肺器官和ex vivo肺损伤模型被用于再生研究.
主要成果:
- 与野生型FGF10相比,工程FGF10-STAB的化温度明显增加.
- 在实验室中,FGF10-STABs的FGF受体结合和信号激活与野生型FGF10相似.
- 在体内,FGF10-STABs与野生型FGF10不同,抑制了肺部分支和改变了四肢形态发生.
- 在受伤模型中,FGF10-STABs增强了肺器官分化和改善了肺再生.
结论:
- 热力学不稳定性是FGF10的关键调节机制,防止子宫外信号传递.
- 稳定FGF10变种保持生物活性,并对肺部和四肢发育产生强烈影响.
- 稳定的FGF10变体有望在再生医学中的治疗应用,特别是用于肺部修复.
相关概念视频
TGF - β Signaling Pathway
7.2K
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...
7.2K
Hedgehog Signaling Pathway
7.3K
The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
7.3K
Regulation of Angiogenesis and Blood Supply
2.5K
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...
2.5K
Notch Signaling Pathway
4.1K
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
4.1K
Intracellular Signaling Affects Focal Adhesions
2.5K
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Some...
2.5K
Canonical Wnt Signaling Pathway
8.6K
The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which...
8.6K


