Weizhong Jin
Hangzhou First People’s Hospital, Zhejiang Province, China
Title: The role of SIRT1 in LPS-induced lung endothelial barrier dysfunction and lung injury in vivo
Biography
Biography: Weizhong Jin
Abstract
The aim of this study was to determine the role of protein deacetylase SIRT1, one of the nicotinamide adenine dinucleotide(NAD+)-dependent intracellular silent information regulators, in lipopolysaccharide (LPS)-induced lung endothelial barrier dysfunction and lung injury in vivo.
Methods
The cultured human pulmonary endothelial cells (HPECs) were exposed to LPS and C57BL/6 mice administered intratracheally, and were treated with SIRT1 activator SRT1720 or inhibitor EX527 after LPS exposure, respectively. The endothelial permeability was measured in transwell by use of FITC-dextra. Lung injury was studied by measuring vascular permeability, histopathological examination, nature of infiltrating cells, inflammatory cytokine induction in the broncho-alveolar fluid.
Results
In cultured HPECs, LPS increased endothelial permeability in parallel with a decrease in SIRT1 expression. Consistent with this observation, SIRT1 activation with the potent sirt1 activator SRT1720 attenuated LPS-induced endothelial hyper-permeability in vitro, but increased by the SIRT1 inhibitor EX527. Intra-tracheal administration of LPS (5 mg/kg) in mice reduced sirts expression in lung tissue extracts, increased protein content and cell count in bronchial alveolar lavage fluid, and increased Evans Blue dye infiltration into the lung. Pretreatment with SRT1720 reduced the lung injury in LPS-treated WT mice, and EX527 accentuated the lung injury.
Conclusions
We concluded that SIRT1 play a role in LPS-induced endothelial barrier dysfunction and that its activation attenuated the endothelial barrier dysfunction and lung injury.