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相关概念视频

Cell-matrix's Response to Mechanical Forces01:13

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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. 
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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...
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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.
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Unlike epithelial tissue, which is composed of cells closely packed with little or no extracellular space in between, connective tissue cells are dispersed in a matrix. This extracellular matrix (ECM) is composed of fibrous proteins like collagen, elastin, and fibronectin in a ground substance consisting of interstitial fluid, cell adhesion proteins, and proteoglycans. The proteoglycans form a gel-like material in the spaces between cells and provide hydration, buffering, binding, and force...
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矩阵刚度会诱导内皮细胞网络衰老.

Jiyeon Song1, Alexandra N Rindone2, Ya Guan1

  • 1Department of Biomedical Engineering, Duke University, Durham, NC 27708, USA.

bioRxiv : the preprint server for biology
|November 24, 2025
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概括

组织硬化驱动内皮细胞中的细胞衰老,影响衰老和疾病. 针对Notch信号通路提供了机械老化的潜在干预.

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科学领域:

  • 细胞衰老 细胞衰老
  • 机械生物学 机械生物学
  • 血管的衰老 血管的衰老

背景情况:

  • 细胞衰老有助于与年龄有关的组织功能障碍.
  • 了解衰老的驱动因素是开发恢复性干预措施的关键.
  • 机械应激在内皮细胞衰老中的作用尚未完全理解.

研究的目的:

  • 研究细胞外矩阵 (ECM) 刚性如何影响内皮细胞 (EC) 衰老.
  • 建立一个模型系统来研究衰老,仅仅是为了应对机械压力.
  • 确定涉及机械诱导EC衰老的分子途径.

主要方法:

  • 开发了一个3D人体体外试验模型,以隔离机械应激效应.
  • 评估了EC衰老标志物 (p16/p21) 和与衰老相关的分泌表型 (SASP).
  • 分析了Notch-JNK-FOS信号轴,并使用药理学Notch抑制.
  • 检查了合成乳房植入物患者的纤维化囊组织.
  • 在患者衍生组织上利用单细胞RNA测序 (scRNA-seq).

主要成果:

  • 矩阵硬化诱导了EC衰老表型,包括高的p16/p21和SASP,没有炎症信号.
  • 一个Notch-JNK-FOS信号轴介导机械诱导衰老.
  • 缺口抑制减弱了硬度诱导的衰老.
  • 患者纤维化组织显示p16+Notch1+内皮细胞增加,富含Notch/JNK和SASP基因程序.
  • 证实组织硬是上游衰老信号,驱动血管衰老.

结论:

  • 血管衰老是一种机械敏感过程,由组织硬化驱动.
  • 在机械诱导的EC衰老中发现了一种新的Notch-JNK-FOS信号通路.
  • 这项研究为研究内皮质机械化和潜在的治疗点提供了一个与人类相关的平台.