Activating Sig-1R inhibits microvascular permeability by reducing LRRK2 expression in lipopolysaccharide-induced acute lung injury

Free Radical Biology and Medicine, Год журнала: 2024, Номер 226, С. 96 - 108

Опубликована: Ноя. 12, 2024

Endothelial cells are the first and most damaged target during acute lung injury (ALI). dysfunction increases pulmonary microvascular permeability, subsequently leading to oedema organ dysfunction; however, clinical treatments against permeability show poor efficacy. Herein, we aimed explore role of Sigma-1 receptor (Sig-1R) in by constructing ALI animal cell models, further investigated specific mechanisms. The effects Sig-1R on endothelial barrier disruption were examined lipopolysaccharide (LPS)-induced mice human umbilical vein (HUVECs), respectively. Transcriptome sequencing was carried out identify possible targets Sig-1R, mechanisms action using RNA interference plasmid transfection. Analysis a Gene expression omnibus dataset suggested that plays protective vascular hyperpermeability ALI. Downregulation both observed HUVECs upon LPS stimulation. agonists attenuated vivo vitro, improving activation downregulated Leucine-rich repeat kinase 2 (LRRK2) HUVECs. LRRK2 knockdown ameliorated Overexpression reversed effect LPS-induced hyperpermeability. Furthermore, Sig1r exacerbated hyperpermeability, which rescued inhibition LRRK2. exerts downregulating expression, could lead development novel therapeutic strategies for treating

Язык: Английский

Ligand docking in the sigma-1 receptor compared to the sigma-1 receptor-BiP complex and the effects of agonists and antagonists on C. elegans lifespans

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 182, С. 117783 - 117783

Опубликована: Дек. 26, 2024

Язык: Английский