KLF2
自噬
脊髓损伤
外渗
血脑屏障
内皮功能障碍
埃文斯蓝
细胞生物学
免疫印迹
脊髓
医学
化学
生物
免疫学
神经科学
内科学
下调和上调
中枢神经系统
生物化学
细胞凋亡
基因
作者
Zili He,Jianyang Du,Yu Zhang,Yitie Xu,Qian Huang,Qing Zhou,Min Wu,Yao Li,Zhaoxiong Xie,Hongyu Zhang,Yuepiao Cai,Keyong Ye,Xiangyang Wang,Yingze Zhang,Qiang Han,Jian Xiao
出处
期刊:Theranostics
[Ivyspring International Publisher]
日期:2023-01-01
卷期号:13 (2): 849-866
被引量:3
摘要
Background: Increasing evidence suggests that acute traumatic spinal cord injury (SCI)-induced defects in autophagy and autophagy-lysosomal pathway (ALP) may contribute to endothelial barrier disruption following injury. Recently, Kruppel-like factor 2 (KLF2) was reported as a key molecular switch on regulating autophagy. Whether KLF2 coordinates endothelial endothelial ALP in SCI is not known. Methods: Genetic manipulations of KLF2 were performed in bEnd.3 cells and SCI model. Western blot, qRT-PCR, immunofluorescence staining and Lyso-Tracker Red staining, Evans blue dye extravasation, behavioral assessment via Basso mouse scale (BMS), electrophysiology and footprint analysis were performed. Results: In SCI, autophagy flux disruption in endothelial cells contributes to TJ proteins degradation, leading to blood-spinal cord barrier (BSCB) impairment. Furthermore, the KLF2 level was decreased in SCI, overexpression of which alleviated TJ proteins loss and BSCB damage, which improve motor function recovery in SCI mice, while knockdown of KLF2 displayed the opposite effects. At the molecular level, KLF2 overexpression alleviated the TJ proteins degradation and the endothelial permeability by tuning the ALP dysfunction caused by SCI and oxygen glucose deprivation (OGD). Conclusions: Endothelial KLF2 as one of the key contributors to SCI-mediated ALP dysfunction and BSCB disruption. KLF2 could be a promising pharmacological target for the management and treatment of SCI.
科研通智能强力驱动
Strongly Powered by AbleSci AI