雌激素受体在呼吸道光滑肌肉细胞迁移中差异性修改了乳和焦点粘附动态
Nilesh Sudhakar Ambhore1, Premanand Balraj1, Christina M Pabelick2
1Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND, USA.
Molecular and cellular endocrinology
|October 12, 2023
概括
雌激素受体β (ERβ) 激活通过影响动因动态和焦点粘附来抑制气道光滑肌细胞迁移. 这表明ERβ是气道改造的潜在治疗点.
科学领域:
- 细胞生物学 细胞生物学
- 内分泌学 在内分泌学.
- 肺部病理学 肺部病理学
背景情况:
- 雌激素信号,特别是17β-雌激醇 (E2),对呼吸道重塑有复杂的影响.
- 以前的研究表明,雌激素受体 (ERα和ERβ) 对呼吸道光滑肌 (ASM) 细胞增殖和细胞外基质产生有差异性影响.
- 在ASM细胞迁移中ERs的作用仍然在很大程度上是未知的.
研究的目的:
- 研究ERα和ERβ在调节血小板衍生生长因子 (PDGF) 诱导的人类ASM细胞迁移中的不同作用.
- 阐明潜在的分子机制,重点关注actin动力学和焦点粘附形成.
主要方法:
- 利用Lionheart-FX自动显微镜和transwell测试来量化ASM细胞迁移.
- 采用shRNA来击败ERα表达和药理学激动剂用于特定的ER激活.
- 分析了使用共聚焦显微镜和图像分析的行为蛋白聚合 (F/G-行为蛋白比),与行为蛋白相关的蛋白质表达 (N-WASP,Arp2/3复合体) 和焦点粘附动力学 (素,帕克西林).
主要成果:
- 特定的ERβ激活,或ERβ激活与ERα淘汰相结合,显著削弱PDGF诱导的ASM细胞迁移.
- ERβ激活抑制了乙聚合,降低了N-WASP和Arp2/3复合物的表达,并降低了焦点粘附集群.
- 激活ERα或治疗E2并没有显著改变actin/lamellipodial动态.
结论:
- 激活ERβ在抑制ASM细胞迁移方面发挥着至关重要的作用,它通过调节活性蛋白聚合,状体形成和焦点粘附动力学来抑制ASM细胞迁移.
- 这些发现突出了ERβ作为减轻气道改造过程的潜在治疗点.
相关概念视频
Intracellular Signaling Affects Focal Adhesions
2.7K
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...
2.7K
Cell-matrix's Response to Mechanical Forces
2.7K
In animal cells, the extracellular matrix allows cells within tissues to withstand external stresses and transmits signals from the outside of the cell to the inside. The extracellular matrix is extensive, and its composition varies between different types of tissues. For example, the reticular fibers and ground substance make up the ECM in loose connective tissue, while collagen and bone minerals make up the ECM of bone tissue.
Anchoring junctions mechanically attach a cell to the...
Anchoring junctions mechanically attach a cell to the...
2.7K
Cytoskeletal Coordination in Cell Migration
4.8K
A migrating cell changes its shape during the cyclic events of attachment and detachment from the substratum and repositions the cell organelles correspondingly. These complex events are orchestrated by the dynamic cytoskeletal network comprising actin filaments, intermediate filaments, and microtubules. Cytoskeletal crosstalk — the direct and indirect communication between the different components — is crucial for this coordination. Direct communication involves various linker...
4.8K
Anchoring Junctions
3.8K
Anchoring junctions are multiprotein complexes that help cells connect to other cells and the extracellular matrix. Anchoring junctions are present on the lateral and basal surfaces of cells, providing strong and flexible connections. Focal adhesions are often formed due to cell interactions with the ECM substrata, which initiate signal transduction via kinase cascades and other mechanisms. Together, they provide stability and tissue integrity. There are three types of anchoring junctions:...
3.8K
Role of Myosin in Cell Migration
2.3K
Myosins are multimeric motor proteins involved in various cellular processes such as migration, adhesion, and proliferation. Myosin II is the most common type in animal cells, which binds and cross-links actin filaments.
Myosin II is a hexamer comprising two heavy chains with globular heads and coiled-coil tails, two regulatory light chains, and two essential light chains. The ATPase sites on the myosin heads hydrolyze ATP, and the released phosphate generates the force for contraction....
Myosin II is a hexamer comprising two heavy chains with globular heads and coiled-coil tails, two regulatory light chains, and two essential light chains. The ATPase sites on the myosin heads hydrolyze ATP, and the released phosphate generates the force for contraction....
2.3K
Cell Migration
4.9K
Cell migration is a process by which the cells move from one location to another, playing an essential role in embryological development, repair and regeneration, immune response, and metastasis. Cells migrate in response to chemical or mechanical signals generated by specific organs or tissues. The overall mechanism includes three steps - polarization, protrusion, and release. Polarization involves the formation of a distinct cell front and rear, which determines the direction of movement.
4.9K


