SIRT1 Is a Novel Regulator of Key Pathways of Human Labor1

Abstract

Human sirtuin (SIRT) 1 and SIRT2, which possess nicotinamide 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 syncytiotrophoblast 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 lipopolysaccharide (LPS) and proinflammatory cytokines TNF and IL1B. The SIRT1 activators resveratrol and SRT1720 significantly decreased LPS-induced TNF, IL6, and IL8 gene expression and release and PTGS2 mRNA expression and resultant prostaglandin (PG) E(2) and PGF(2α) release from human gestational tissues. In conclusion, SIRT1 possesses anti-inflammatory actions and thus may play a role in regulating pregnancy and parturition.

Weakening and Rupture of Human Fetal Membranes – Biochemistry and Biomechanics

“…TIMP-1 was barely detectable; TIMP-2 and TIMP-4 protein were detectable in all specimens but did not change with Strength. Other groups have also confirmed the increase in markers of collagen remodeling and apoptosis (Malak & Bell et al, 1994;El-Khwad et al, 2005Meinert et al, 2007, Reti et al, 2007Han et al, 2008;Lappas et al, 2008Lappas et al, , 2009Lappas et al, , 2010aLappas et al, , 2010b. Using FM from patients with AROM (artificial rupture of membranes) and SROM (spontaneous rupture of membranes), we have further demonstrated that the para-cervical weak zone persists with the same biochemical signature as that identified in pre-labor cesarean section membranes.…”

The effect of leptin and resveratrol on JAK/STAT pathways and Sirt-1 gene expression in the renal tissue of ischemia/reperfusion induced rats

“…SIRT1 plays a pivotal role in regulation of NF-κB-dependent proinfl ammatory mediator expression. Many studies in different tissues have shown that effects of resveratrol are via modulation of NF-κB (17). Although these effects have been confi rmed in in vitro studies (5,7), there are no in vivo studies investigating the role of SIRT1 gene expression in renal I/R injury.…”

KLF5 regulates infection- and inflammation-induced pro-labour mediators in human myometrium

“…Foetal membranes from the non-labouring group were obtained from the supracervical site (SCS). Identification of the SCS was performed as previously detailed (Lappas et al 2011). Briefly, Bonneys blue dye was introduced through the cervix before Caesarean section.…”

“…Upon delivery of the placenta, a blue mark was obvious on the chorion-facing membrane where the dye had been applied. In the after-labour group, foetal membranes from the site of membrane rupture (SOR) as previously described (Lappas et al 2011). Amnion and underlying choriodecidua were collected from along the line of foetal membrane rupture.…”