SIRT1 protects rat lung tissue against severe burn-induced remote ALI by attenuating the apoptosis of PMVECs via p38 MAPK signaling.
SIRT1 protects rat lung tissue against severe burn-induced remote ALI by attenuating the apoptosis of PMVECs via p38 MAPK signaling.
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DOI：
10.1038/srep10277
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发表时间：
2015-05-20
影响因子：
4.6
通讯作者：
Hu D
中科院分区：
文献类型：
--
作者：
Bai X;Fan L;He T;Jia W;Yang L;Zhang J;Liu Y;Shi J;Su L;Hu D
沉默信息调节因子-1(SIRT1)参与心肺保护。然而，其在烧伤后远端急性肺损伤(ALI)发病机制中的作用目前尚不清楚。本研究旨在探讨SIRT1在烧伤后远端ALI中的作用及其信号转导途径。我们观察到烧伤后大鼠肺组织中SIRT1的表达在短时间内呈上升趋势。白藜芦醇刺激SIRT1表达上调，严重烧伤大鼠肺组织病理改变减轻，细胞凋亡减少，促炎细胞因子表达下调。接下来，我们利用烧伤血清(BS)刺激的原代肺微血管内皮细胞(PMVECs)模拟烧伤后大鼠肺组织，发现BS显著抑制SIRT1的表达，增加细胞凋亡，并激活p38MAPK信号转导通路。白藜芦醇的使用逆转了这些效应，而shRNA下调SIRT1进一步增强了BS诱导的细胞凋亡和p38MAPK的激活。综上所述，SIRT1可能通过p38MAPK信号通路抑制PMVEC的凋亡，从而保护肺组织免受烧伤后远期ALI的影响，提示SIRT1对ALI有潜在的治疗作用。
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.
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影响因子：
8
作者：
Becatti, Matteo;Taddei, Niccolo;Fiorillo, Claudia
通讯作者：
Fiorillo, Claudia
影响因子：
4.4
作者：
Kao, Chung-Lan;Chen, Liang-Kung;Hwang, Shin-Jang
通讯作者：
Hwang, Shin-Jang
DOI：
10.1006/bbrc.2000.3000
发表时间：
2000-07-05
影响因子：
3.1
作者：
Frye, RA
通讯作者：
Frye, RA
DOI：
10.1097/ta.0b013e3182127d48
发表时间：
2011-11-01
影响因子：
--
作者：
Fang, Yong;Xu, Peng;Yao, Min
通讯作者：
Yao, Min
影响因子：
5.4
作者：
Du, Gang;Song, Yunlin;Li, Zicheng
通讯作者：
Li, Zicheng