SIRT1 negatively regulates invasive and angiogenic activities of the extravillous trophoblast

Abstract

ProblemDysregulation of extravillous trophoblast (EVT) invasion leads to pregnancy complications, such as pre‐eclampsia, fetal growth restriction, and placenta accreta. The aim of this study was to explore the role of SIRT1 in EVT invasion and its underlying mechanism.Method of studySIRT1‐specific siRNA was transfected into Swan 71 cells, an immortalized first trimester trophoblast cell line. The Boyden chamber invasion assay, the scratch wound healing assay, and cell proliferation assay were performed. The expression levels of epithelial‐to‐mesenchymal transition (EMT) markers, matrix metalloproteinase‐2 (MMP‐2), MMP‐9, p‐Akt, Akt, p‐p38MAPK, p38MAPK, p‐ERK, ERK, p‐JNK, JNK, Fas, and Fas ligand (FasL) were examined by western blot. Tube formation assay was conducted by using Matrigel.ResultsSIRT1 knockdown by siRNA significantly enhanced invasion and migration as well as the expression of MMP‐2, MMP‐9, and EMT markers in Swan 71 cells, but reduced proliferation. The effects of SIRT1 knockdown on invasion, migration, proliferation, and endothelial‐like tube formation in Swan 71 cells were reversely regulated by blockade of Akt and p38MAPK signaling. In addition, SIRT1 knockdown markedly promoted colocalization of Swan 71 cells to human umbilical vein endothelial cell (HUVEC) networks and induced reduction in Fas and enhancement of FasL. Conditioned media of SIRT1 knockdown‐Swan 71 cells caused reduction in cell proliferation and augmentation of cytotoxicity along with increased Fas expression in HUVECs.ConclusionOur results suggest that SIRT1 may be associated with placental development by controlling EVT invasion and spiral artery remodeling via modulation of EMT, MMP‐2, MMP‐9, Akt/p38MAPK signaling, and Fas/FasL.

Resveratrol drives cancer cell senescence via enhancing p38MAPK and DLC1 expressions

“…The effects of SIRT1 knockdown on invasion, migration, proliferation and endotheliallike tube formation are regulated reversely by the blockade of p38MAPK signaling in human trophoblast cells. 20 Considering that p38MAPK intensifies ER stress both in vitro and in vivo, 21,22 we speculate that resveratrol induces ER stress through the SIRT1/p38MAPK signaling pathway. To test this hypothesis, the expressions of SIRT1, p38MAPK and its active form phosphorylated p38 ( p-p38MAPK) were detected in MCF-7 and NCI-H1299 cells without or with 100 μM resveratrol treatment for 24 h, and the western blot results showed that resveratrol increased their protein levels (Fig.…”

[Retracted] Clinical Value of Serum SIRT1 Combined with Uterine Hemodynamics in Predicting Disease Severity and Fetal Growth Restriction in Preeclampsia

“…Trophoblast invasion is regulated by various pathways and factors, among which SIRT1 is involved in regulating various biological processes [27]. SIRT1, a member of the NAD + -dependent protein deacetylase family and a nutrient sensor, was originally discovered in the genome of budding Saccharomyces cerevisiae, a gene that regulates lifespan and was frst identifed as a histone deacetylase that promotes chromatin compaction and thus silences the genome during nutrient deprivation [28].…”

Effects of Maternal Resveratrol on Maternal High-Fat Diet/Obesity with or without Postnatal High-Fat Diet

“…AKT signaling pathway interacts with insulin and the mammalian target of rapamycin, and is linked with fetoplacental vascular development [32]. SIRT1 is associated with placental development by controlling extravillous trophoblast invasion and spiral artery remodeling [33]. Adiponectin contributes to the hormonal control of fetal growth and is involved in compromised pregnancy [34].…”