Activation of SIRT1 ameliorates LPS-induced lung injury in mice via decreasing endothelial tight junction permeability.

Acta Pharmacologica Sinica
Cuiping FuShanqun Li

Abstract

The integrity of the endothelial barrier is a determinant of the prognosis of lipopolysaccharide (LPS)-induced acute lung injury (ALI). In this study, we investigated whether and how Sirtuin 1 (SIRT1) maintained the vascular integrity during ALI. An experimental model of ALI was established in mice through intratracheal administration of LPS (10 mg/kg). LPS stimulation significantly increased the pulmonary permeability and decreased the expression of SIRT1 and tight junction proteins (TJs), including occludin, claudin-5, tight junction protein 1 and tight junction protein 2. Morphological studies showed that LPS induced obvious lung injury with inflammatory cell infiltration in the interstitial and alveolar space, hemorrhage, edema, and the thickened alveolar wall compared to the control mice. Intratracheal administration of the selective SIRT1 activator SRT1720 (6.25 mg/kg) significantly attenuated LPS-induced lung injury, lung hyper-permeability and increased TJs expression, whereas intratracheal administration of the selective SIRT1 inhibitor EX527 (6.25 mg/kg) aggravated LPS-induced ALI. Similar protective effects of SIRT1 on pulmonary cellular permeability were observed in primary human pulmonary microvascular endothelial ...Continue Reading

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Citations

Oct 23, 2019·World Journal of Gastroenterology : WJG·Meng-Ting RenChen-Yan Ding
Oct 14, 2020·Molecular Metabolism·Carmen Escalona-GarridoÁngela M Valverde
Sep 17, 2021·Cardiovascular Research·E V DolmatovaK K Griendling
Oct 5, 2021·Experimental and Therapeutic Medicine·Xianfeng Chen, Juanjuan Huang
Dec 3, 2021·European Journal of Histochemistry : EJH·Chunlin YeGuowen Zou

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Methods Mentioned

BETA
Transfection
PCR
Protein Assay
electrophoresis

Software Mentioned

GraphPad Prism
GraphPad

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