时间调节Ihh-PTHrP信号轴通过血管新生来调节状腺发育
Chuanqing Mao1, Yunpeng Weng2, Wenjie Zhou1
1Department of Oral and Maxillofacial Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China.
Differentiation; research in biological diversity
|January 15, 2026
概括
维斯莫德吉布药物通过抑制"刺"信号来破坏关节 (TMJ) 发育,导致小鼠的状腺生长减少和血管生成发生变化.
科学领域:
- 发育生物学是发展生物学.
- 头骨面部形态发生.
- 药理学 药理学是指药理学的学科.
背景情况:
- 维斯莫迪吉布 (Smoothened受体对抗剂) 抑制了对 Hedgehog 的信号传递,影响了胚胎的发育.
- 它在关节 (TMJ) 发育中的作用尚不清楚.
研究的目的:
- 在小鼠模型中研究vismodegib对胎儿TMJ发育的影响.
- 阐明维斯莫迪吉布诱导的TMJ发育改变背后的分子机制.
主要方法:
- 怀孕的小鼠在胚胎日14.5.5接受一次剂量vismodegib (150毫克/公斤).
- 关节形态,细胞增殖 (PHH3),细胞亡 (TUNEL) 和血管生成标志物 (VEGF,CD31,CD34) 在产后被评估.
- 分析了Ihh-PTHrP信号通路组件 (Gli1,Ptch1,PTHrP) 的表达在E15.5.5.
主要成果:
- 维斯莫迪吉布治疗导致骨长度和骨表面积密度显著减少.
- 没有观察到细胞增殖或细胞亡的变化.
- 血管新生标志物上调,而Ihh-PTHrP信号元件在暴露于vismodegib的TMJ中下调.
结论:
- 维斯莫德吉布通过抑制Ihh-PTHrP通路来损害关节的发育.
- 这种抑制会改变状血管生成,影响软骨生长和结构完整性.
- 这些发现凸显了vismodegib破坏面发育的潜力.
相关概念视频
Regulation 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
Hedgehog Signaling Pathway
9.8K
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...
9.8K
TGF - β Signaling Pathway
10.5K
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...
10.5K
Bone Formation by Endochondral Ossification
8.4K
Bone formation, or ossification, begins around the sixth to seventh week of embryonic development. Most bones develop from a cartilaginous template through the process of endochondral ossification. Cartilage formation begins when clusters of mesenchymal cells differentiate into chondrocytes. These chondrocytes proliferate rapidly and secrete an extracellular matrix that becomes encased in a membrane called the perichondrium. The resulting cartilage model provides a template that resembles the...
8.4K
Regulation of Hematopoietic Stem Cells
4.0K
All blood and immune cells are produced from the multipotent hematopoietic stem cells (HSCs) by the process of hematopoiesis. However, they all have a limited life span. In addition, many are depleted in immune surveillance or combatting an injury or infection. This makes blood one of the most regenerative tissues. Hematopoiesis helps replenish these blood and immune cells, restoring the body's normal functioning. However, overproduction of blood and immune cells can make them cancerous or...
4.0K
Role Of Notch Signalling In Intestinal Stem Cell Renewal
2.4K
Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
2.4K


