Abstract
Silent information regulator type-1 (SIRT1) has been reported to be involved in the cardiopulmonary protection. However, its role in the pathogenesis of burn-induced remote acute lung injury (ALI) is currently unknown. The present study aims to investigate the role of SIRT1 in burn-induced remote ALI and the involved signaling pathway. We observed that SIRT1 expression in rat lung tissue after burn injury appeared an increasing trend after a short period of suppression. The upregulation of SIRT1 stimulated by resveratrol exhibited remission of histopathologic changes, reduction of cell apoptosis, and downregulation of pro-inflammatory cytokines in rat pulmonary tissues suffering from severe burn. We next used primary pulmonary microvascular endothelial cells (PMVECs) challenged by burn serum (BS) to simulate in vivo rat lung tissue after burn injury, and found that BS significantly suppressed SIRT1 expression, increased cell apoptosis, and activated p38 MAPK signaling. The use of resveratrol reversed these effects, while knockdown of SIRT1 by shRNA further augmented BS-induced increase of cell apoptosis and activation of p38 MAPK. Taken together, these results indicate that SIRT1 might protect lung tissue against burn-induced remote ALI by attenuating PMVEC apoptosis via p38 MAPK signaling, suggesting its potential therapeutic effects on the treatment of ALI.
Highlights
Sirtuins, the class III nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases, are emerging regulators of various biological processes[8]
Results showed that silent information regulator type-1 (SIRT1) mRNA level was slightly suppressed at the early stage at 1 h post-burn and significantly increased by approximately 2-fold at 3 h and lasted till 24 h post-burn (Fig. 1A); SIRT1 protein level showed the same trend except that the early suppressive effect appeared at both 1 h and 3 h post-burn, and the upregulation of SIRT1 began at 6 h and lasted till 24 h post-burn injury (Fig. 1B)
We moved to assess the effect of resveratrol, a known SIRT1 activator, on the morphological changes of rat lung tissue after burn injury by hematoxylin and eosin (H&E) staining
Summary
The class III nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases, are emerging regulators of various biological processes[8]. SIRT1 has been shown to play a role in transcriptional and post-transcriptional regulation of gene expression through the deacetylation of histone and non-histone proteins[8]. Recent studies have shown that resveratrol leads to the amelioration of staphylococcal enterotoxin B-induced lung injury[21] and attenuates the apoptosis of pulmonary microvascular endothelial cells (PMVECs) induced by high shear stress and pro-inflammatory factors[22]. We have shown that resveratrol exerted protective roles in rat lung after severe burn injury by modulating SIRT1 expression. Our results have demonstrated that the protective effect of resveratrol on lung tissue might be through attenuating the inflammatory damage and PMVEC apoptosis by inhibiting p38 mitogen activated protein kinase (MAPK) pathway
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