基质变硬通过 PI3K/Akt/mTOR 通路促进 VEGF-A 的功能。
Substrate stiffening promotes VEGF-A functions via the PI3K/Akt/mTOR pathway.
机构信息
Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA; Innovation and Incubation Centre for Entrepreneurship, IISER, Bhopal, MP, 462066, India; Centre for Science and Society, IISER, Bhopal, MP, 462066, India.
Schepens Eye Research Institute at Massachusetts Eye and Ear, Boston, MA, 02114, USA.
出版信息
Biochem Biophys Res Commun. 2022 Jan 1;586:27-33. doi: 10.1016/j.bbrc.2021.11.030. Epub 2021 Nov 13.
Abstract
While it is now well-established that substrate stiffness regulates vascular endothelial growth factor-A (VEGF-A) mediated signaling and functions, causal mechanisms remain poorly understood. Here, we report an underlying role for the PI3K/Akt/mTOR signaling pathway. This pathway is activated on stiffer substrates, is amplified by VEGF-A stimulation, and correlates with enhanced endothelial cell (EC) proliferation, contraction, pro-angiogenic secretion, and capillary-like tube formation. In the settings of advanced age-related macular degeneration, characterized by EC and retinal pigment epithelial (RPE)-mediated angiogenesis, these data implicate substrate stiffness as a novel causative mechanism and Akt/mTOR inhibition as a novel therapeutic pathway.
摘要
虽然现在已经确定，基质硬度调节血管内皮生长因子 A（VEGF-A）介导的信号和功能，但是因果机制仍知之甚少。在这里，我们报告了 PI3K/Akt/mTOR 信号通路的基础作用。该途径在较硬的基质上被激活，通过 VEGF-A 刺激放大，并与增强的内皮细胞（EC）增殖、收缩、促血管生成分泌和毛细血管样管状形成相关。在以 EC 和视网膜色素上皮（RPE）介导的血管生成为特征的老年相关性黄斑变性的背景下，这些数据表明基质硬度是一种新的致病机制，Akt/mTOR 抑制是一种新的治疗途径。
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