在纤维生成过程中,明丁通过独特的Src家族激酶调节纤维细胞亚群
Sunny Kataria1,2,3, Isha Rana1,4, Krithika Badarinath1,3
1IFOM-inStem Joint Research Laboratory, Centre for Inflammation and Tissue Homeostasis, Institute for Stem Cell Science and Regenerative Medicine (inStem), Bangalore, Karnataka, India.
JCI insight
|December 31, 2024
概括
敏丁通过差异调节不同的亚群来协调皮肤纤维化中的纤维细胞异质性. 这种蛋白质影响迁移,炎症,收缩性和原蛋白的产生,影响纤维性疾病和癌症.
科学领域:
- 皮肤病学 皮肤病学
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 纤维化涉及过度的细胞外基质 (ECM) 沉积,导致组织硬和器官功能障碍.
- 激活的纤维细胞是纤维化中的关键参与者,表现出各种功能,如迁移,增殖,收缩和ECM生产.
- 纤维细胞异质性表明子群可能具有专门的角色和独特的调节控制.
研究的目的:
- 调查不同的纤维细胞亚群是否负责纤维化中的特定激活过程.
- 确定敏丁 (spondin-2) 在皮肤纤维化期间调节纤维细胞异质性的作用.
- 在癌症相关纤维细胞的背景下,探索明丁对纤维细胞亚群的影响.
主要方法:
- 利用皮肤纤维化的转基因小鼠模型.
- 研究了牛转基因角质细胞分泌的明丁对皮肤纤维细胞亚群的影响.
- 分析了信号通路,包括Fyn激酶和c-Src,参与了明丁的差异调节.
主要成果:
- 敏丁差异调节纤维细胞亚群,通过Fyn激酶促进SCA1+纤维细胞中的迁移和炎症基因表达.
- 敏丁通过c-Src信号来增强乳头CD26+纤维细胞的收缩性和原蛋白的产生.
- 纤维细胞亚群中对Mindin的不同反应延伸到功能异质的癌症相关纤维细胞的产生.
结论:
- 敏丁被认为是皮肤纤维细胞异质性在皮肤纤维化中的关键协调者.
- 敏丁重新塑造纤维微环境中的细胞动力学和信号多样性.
- 了解Mindin的作用为我们提供了关于纤维瘤疾病和癌症流体生物学的见解.
相关概念视频
Introduction to Fibroblasts
3.0K
Rudolph Virchow discovered spindle-shaped cells called fibroblasts in 1858. Inactive fibroblasts, called fibrocytes, become activated by various stimuli, such as growth factors and inflammatory cytokines. Activated fibroblasts play a crucial role in wound healing, inflammation, formation of new blood vessels, and cancer progression. Uncontrolled activation of fibroblasts results in fibrosis, the excess deposition of fibrous tissue, which can lead to scarring and affect normal organs. This...
3.0K
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
Intracellular Signaling Affects Focal Adhesions
2.6K
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...
2.6K
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
MAPK Signaling Cascades
5.2K
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
5.2K
Mitogens and the Cell Cycle
6.4K
Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
6.4K


