中性粒细胞胞外陷阱靶向衰老血管系统在视网膜病变组织重塑中的作用
2020-08-23   阅读:1324   来源:科学

加拿大蒙特利尔眼科Przemyslaw Sapieha研究团队近日取得一项新成果。经过不懈努力,他们揭示了中性粒细胞胞外陷阱目标衰老血管在视网膜病变组织重塑中的作用。 2020年8月21日出版的《科学》发表了这项成果。

研究团队对患有增生性糖尿病性视网膜病变的人类患者和缺血性视网膜病变的小鼠模型使用正交方法,鉴定嗜中性粒细胞在晚期无菌炎症过程中血管重构中的非常规作用。衰老的血管系统释放了一个吸引中性粒细胞并触发中性粒细胞胞外诱捕器(NETs)产生的分泌组。

NET最终清除了患病的内皮细胞并改造了不健康的血管。 NETosis的遗传或药理抑制作用阻止衰老血管的退化和疾病的延长。因此,清除衰老的视网膜血管会导致修复性血管重塑。

研究人员表示,在发达国家失明的主要原因是糖尿病性视网膜病等血管系统紊乱,可能会纤维化。尽管许多此类病理性血管通常会自然退缩并避免视力受损的并发症,但其潜在机制仍然未知。本研究提供了基本理解。

附:英文原文

Title: Neutrophil extracellular traps target senescent vasculature for tissue remodeling in retinopathy

Author: Franois Binet, Gael Cagnone, Sergio Crespo-Garcia, Masayuki Hata, Mathieu Neault, Agnieszka Dejda, Ariel M. Wilson, Manuel Buscarlet, Gaelle Tagne Mawambo, Joel P. Howard, Roberto Diaz-Marin, Celia Parinot, Vera Guber, Frédérique Pilon, Rachel Juneau, Rémi Laflamme, Christina Sawchyn, Karine Boulay, Severine Leclerc, Afnan Abu-Thuraia, Jean-Franois Cté, Gregor Andelfinger, Flavio A. Rezende, Florian Sennlaub, Jean-Sébastien Joyal, Frédérick A. Mallette, Przemyslaw Sapieha

Issue&Volume: 2020/08/21

Abstract: In developed countries, the leading causes of blindness such as diabetic retinopathy are characterized by disorganized vasculature that can become fibrotic. Although many such pathological vessels often naturally regress and spare sight-threatening complications, the underlying mechanisms remain unknown. Here, we used orthogonal approaches in human patients with proliferative diabetic retinopathy and a mouse model of ischemic retinopathies to identify an unconventional role for neutrophils in vascular remodeling during late-stage sterile inflammation. Senescent vasculature released a secretome that attracted neutrophils and triggered the production of neutrophil extracellular traps (NETs). NETs ultimately cleared diseased endothelial cells and remodeled unhealthy vessels. Genetic or pharmacological inhibition of NETosis prevented the regression of senescent vessels and prolonged disease. Thus, clearance of senescent retinal blood vessels leads to reparative vascular remodeling.

DOI: 10.1126/science.aay5356

编辑:小柯机器人

©2022年12月07日 09:06:38
基因在线
0.1537s加载完成
邮箱:info@jiyinzaixian.com