TSP2 缺陷促进纤维细胞的增殖和迁移,增强了 WNT4/β-catenin/TGFb3 的作用.
Yaqing Huang1,2, Hao Xing2,3, Jingru Tian4
1Department of Pathology, Yale University, New Haven, Connecticut, USA.
概括
移除Thrombospondin-2 (TSP2) 增强纤维细胞功能,促进组织修复. 缺少TSP2可以提高重点再生途径的调节,这表明TSP2是慢性伤口的治疗点.
科学领域:
- 细胞生物学 细胞生物学
- 伤口治愈研究研究 伤口治愈研究
- 生物化学 生物化学
背景情况:
- 慢性伤口是由于纤维细胞功能受损和细胞外基质 (ECM) 重塑而造成的重大医疗保健挑战.
- 众所周知,一种母细胞糖蛋白的Thrombospondin-2 (TSP2) 阻碍了伤口愈合过程.
研究的目的:
- 研究皮肤纤维细胞中TSP2缺乏的细胞和转录基因影响.
- 阐明TSP2在调节纤维细胞行为和组织修复过程中的ECM相互作用中的作用.
主要方法:
- 大量RNA测序是在野生型 (WT) 和TSP2淘汰 (TSP2KO) 鼠原发性纤维细胞上进行的.
- 使用CRISPR/Cas9基因编辑,在NIH3T3纤维细胞中创建稳定的TSP2淘汰,以进行可靠的模型验证.
主要成果:
- TSP2 缺乏导致了亲再生分子和信号通路的上调,包括TGF-β3和Wnt4/β-catenin.
- 在工程细胞模型中,TSP2枯竭增强了纤维细胞的增殖和迁移.
- 在TSP2缺陷纤维细胞中观察到TGF-β3和Wnt/β-catenin信号通路的活性增加.
结论:
- TSP2负面调节纤维细胞功能和ECM重塑,影响伤口愈合.
- 准TSP2为增强慢性和受损伤愈合的再生提供了一个潜在的治疗策略.
更多相关视频
06:54Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
14.1K
11:38Visualization and Quantification of TGFβ/BMP/SMAD Signaling under Different Fluid Shear Stress Conditions using Proximity-Ligation-Assay
Published on: September 14, 2021
3.7K
相关概念视频
TGF - β Signaling Pathway
10.4K
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...
10.4K
Canonical Wnt Signaling Pathway
10.3K
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...
10.3K
Non-Canonical Wnt Signaling Pathways
8.2K
Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
8.2K
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal
2.6K
Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
2.6K
The JAK-STAT Signaling Pathway
11.8K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
11.8K
