PDGF信号控制胰腺β细胞的年龄相关增殖
Hainan Chen1, Xueying Gu, Yinghua Liu
1Department of Developmental Biology, Stanford University School of Medicine, Stanford, California 94305, USA.
Nature
|October 14, 2011
概括
血小板衍生生长因子受体 (Pdgfr) 信号控制与年龄相关的胰腺β细胞增殖的下降. 在年轻细胞中激活这种通路促进β细胞扩张,提供潜在的糖尿病治疗方法.
科学领域:
- 再生生物学 再生生物学
- 内分泌学 在内分泌学.
- 发展生物学 发展生物学
背景情况:
- 胰腺β细胞复制对于维持葡萄糖平衡至关重要,并且随着年龄的增长而下降.
- 了解这种衰退背后的机制是开发糖尿病治疗的关键.
- 血小板衍生生长因子受体 (Pdgfr) 信号传导与细胞生长和发育有关.
研究的目的:
- 调查Pdgfr信号传导在依赖年龄的β细胞增殖中的作用.
- 确定诱导β细胞扩张的策略,用于糖尿病治疗.
主要方法:
- 在不同年龄段的老鼠和人类胰腺小岛中研究了Pdgfr信号.
- 在β细胞中利用了Pdgfra的条件基因失活.
- 研究了针对性PDGFR-α激活对β细胞增殖和下游信号通路 (Erk1/2,Ezh2) 的影响.
主要成果:
- 贝塔细胞Pdgfr水平的年龄相关下降与降低的Ezh2水平和增殖相关.
- 在小鼠中,β细胞特异性Pdgfra无活化损害了新生儿扩张和成人再生.
- 在小鼠β细胞中的PDGFR-α激活刺激了Erk1/2酸化和Ezh2-依赖的β细胞扩张.
- 年轻人群岛,但不是成年人群岛,通过增加β细胞增殖来对PDGF-AA作出反应.
结论:
- Pdgfr信号传递是受年龄影响的β细胞增殖的保守调节者.
- 针对Pdgfr信号提供了一种新的治疗策略,用于诱导糖尿病患者的β细胞扩张.
- 年龄和发育阶段会影响β细胞对PDGF信号的响应.
更多相关视频
07:44Surgical Injury to the Mouse Pancreas through Ligation of the Pancreatic Duct as a Model for Endocrine and Exocrine Reprogramming and Proliferation
Published on: August 7, 2015
06:33Optimized Protocol for Generating Functional Pancreatic Insulin-secreting Cells from Human Pluripotent Stem Cells
Published on: February 2, 2024
相关概念视频
01:16TGF - β Signaling Pathway
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 are of three kinds RI, RII, and RIII. The RI...
01:22iPS Cell Differentiation
The ability of induced pluripotent stem cells or iPSCs to differentiate into most body cell types has stimulated repair and regenerative medicine research over the past few decades. iPSC-derived blood cells, hepatocytes, beta islet cells, cardiomyocytes, neurons, and other cell types can repair injuries or regenerate damaged tissue in diseases such as diabetes and neurodegenerative disorders.
01:12Role Of Notch Signalling In Intestinal Stem Cell Renewal
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...