SIRT1 Is a Novel Regulator of Key Pathways of Human Labor
SIRT1 Is a Novel Regulator of Key Pathways of Human Labor
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DOI：
10.1095/biolreprod.110.086983
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发表时间：
2011-01-01
影响因子：
3.6
通讯作者：
Permezel, Michael
中科院分区：
文献类型：
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作者：
Lappas, Martha;Mitton, Amberlee;Permezel, Michael
具有烟酰胺腺苷二核苷酸（NAD（+））依赖性脱乙酰酶活性的人swim（SIRT）1和SIRT 2表现出抗炎作用。然而，没有关于SIRT 1和SIRT 2在人子宫内组织中表达和调节的数据。本研究的目的是表征SIRT 1和SIRT 2在1）足月自然分娩开始之前和之后的胎盘和胎膜，2）来自大脑上部位（SCS）和远端部位（DS）的分娩前胎膜，和3）对促炎刺激的反应。此外，还评估了使用白藜芦醇和SRT 1720的SIRT活化对促分娩介质的作用。SIRT 1和SIRT 2定位于胎盘的合体滋养层和细胞滋养层，羊膜上皮，绒毛膜的滋养层和蜕膜细胞另外，在胎盘血管的内皮壁内发现SIRT 2。与DS相比，在从SCS获得的羊膜和绒毛膜中，SIRT 2而不是SIRT 1染色显著较低。另一方面，在胎盘、羊膜中，SIRT 1而不是SIRT 2基因和/或蛋白表达显著较低，与分娩前相比，分娩后获得的绒毛膜中SIRT 1的表达被脂多糖（LPS）和促炎细胞因子TNF和IL-1B下调，而SIRT 2的表达没有下调。SIRT 1激活剂白藜芦醇和SRT 1720显著降低LPS诱导的TNF，IL-6，和IL 8 β 1表达和释放以及PTGS 2 mRNA表达和产生的人妊娠组织中的前列腺素（PG）E-2和PGF（2 α）释放总之，SIRT 1具有抗炎作用，因此可能在调节妊娠和分娩中起作用
Human swim (SIRT) 1 and SIRT2, which possess nicotin amide adenosine dinucleotide (NAD(+))-dependent deacetylase activity, exhibit anti-inflammatory actions However, there are no data available on SIRT1 and SIRT2 expression and regulation in human intrauterine tissues Thus, the aim of this study was to characterize the localization and expression of SIRT1 and SIRT2 in 1) placenta and fetal membranes before and after term spontaneous labor onset, 2) prelabor fetal membranes from the supracervical site (SCS) and a distal site (DS), and 3) in response to proinflammatory stimuli Further, the effect of SIRT activation using resveratrol and SRT1720 on prolabor mediators was also assessed SIRT1 and SIRT2 were localized in the syncytiotro phoblast layer and the cytotrophoblasts of the placenta, amnion epithelium, trophoblast layer of the chorion, and decidual cells Additionally, SIRT2 was found within the endothelial walls of placental vessels SIRT2, but not SIRT1, staining was significantly lower in amnion and chorion obtained from the SCS compared to a DS On the other hand, SIRT1, but not SIRT2, gene and/or protein expression was significantly lower in placenta, amnion, and chorion obtained after labor compared to prelabor SIRT1 expression, but not SIRT2, was down regulated by lipopolysac charide (LPS) and proinflammatory cytokines TNF and IL1B The SIRT1 activators resveratrol and SRT1720 significantly de creased LPS induced TNF, IL6, and IL8 gale expression and release and PTGS2 mRNA expression and resultant prostaglan din (PG) E-2 and PGF(2 alpha), release from human gestational tissues In conclusion, SIRT1 possesses anti-inflammatory actions and thus may play a role in regulating pregnancy and parturition