An Autophagy-Associated MITF-GAS5-miR-23 Loop Attenuates Vascular Oxidative and Inflammatory Damage in Sepsis.

ABSTRACT:

Background

Sepsis induces GAS5 expression in the vascular endothelium, but the molecular mechanism is unclear, as is the role of GAS5 in sepsis.

Methods and results

We observed that GAS5 expression in the endothelium was significantly upregulated in a sepsis mouse model. ChIP-PCR and EMSA confirmed that the oxidative stress (OS)-activated MiT-TFE transcription factor (MITF, TFE3, and TFEB)-mediated GAS5 transcription. In vitro, GAS5 overexpression attenuated OS and inflammation in endothelial cells (ECs) while maintaining the structural and functional integrity of mitochondria. In vivo, GAS5 reduced tissue ROS levels, maintained vascular barrier function to reduce leakage, and ultimately attenuated sepsis-induced lung injury. Luciferase reporter assays revealed that GAS5 pro

SUBMITTER: Cheng J 

PROVIDER: S-EPMC10376991 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature