Involvement of follistatin-like 3 in preeclampsia

Xie, Jiamin; Xu, Yuqing; Wan, Ling; Wang, Peng; Wang, Miaomiao; Dong, Minyue

doi:10.1016/j.bbrc.2018.10.139

Cited by 30 publications

(29 citation statements)

References 35 publications

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“…3, Additional file 4: Table S3). FSTL3 expression is enhanced by hypoxia and plays a role in trophoblast differentiation, migration and invasion [39, 40]. INHA also plays a role in trophoblast differentiation, and syncytial fusion [41–43].…”

Section: Discussionmentioning

confidence: 99%

Placental microRNAs in pregnancies with early onset intrauterine growth restriction and preeclampsia: potential impact on gene expression and pathophysiology

2019

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Background: A normally developed placenta is integral to a successful pregnancy. Preeclampsia (PE) and intrauterine growth restriction (IUGR) are two common pregnancy related complications that maybe a result of abnormal placental development. Placental microRNAs (miRNAs) have been investigated as potential biomarkers for these complications, as they may play a role in placental development and pathophysiology by influencing gene expression. The purpose of this study is to utilize next-generation sequencing to determine miRNA and gene expression in human placental (chorionic villous) samples from three distinct patient groups with early-onset (EO) PE, IUGR, or PE + IUGR. Methods: Placental tissues were collected from four patient groups (control [N = 21], EO-PE [N = 20], EO-IUGR [N = 18], and EO-PE + IUGR [N = 20]), and total RNA was used for miRNA and RNA sequencing on the Illumina Hiseq2000 platform. For stringent differential expression analysis multiple analysis programs were used to analyze both expression datasets in each patient group compared to gestational age-matched controls.Results: Analysis revealed miRNAs and genes that are disease-specific, as well as others that were common between disease groups, which suggests common underlying placental pathologies in EO-PE and EO-IUGR. More specifically, 6 miRNAs and 22 genes were identified to be differentially expressed in all three patient groups. In addition, integrative analysis between the miRNA and gene expression datasets revealed candidate gene targets for miRNAs of interest. Conclusions: Integration of miRNA and RNA profiling in the same three subgroups of pregnancy complications, provides an alternate level of molecular information, in addition it can be used to better understand both unique and common molecular mechanisms involved in the pathophysiology of these diseases.

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Section: Discussionmentioning

confidence: 99%

Placental microRNAs in pregnancies with early onset intrauterine growth restriction and preeclampsia: potential impact on gene expression and pathophysiology

2019

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“…Data obtained from clinical samples showed that FSTL-3 was elevated in the second trimester, which was associated with an increased risk in developing preeclampsia (Founds et al, 2015). Furthermore, we have demonstrated that the expression of FSTL3 is upregulated in trophoblasts under the stimulus of hypoxia (one of features of preeclampsia) and that the lack of FSTL3 inhibits trophoblast invasion (Xie et al, 2018). These findings indicate that GDF8 and FSTL3 might play a role in the regulation of normal placentation and in preeclampsia.…”

Section: Introductionmentioning

confidence: 61%

“…In our previous studies, we observed that the serum levels and placental expression of FSTL3 were significantly increased in women with preeclampsia (Han et al, 2014). Moreover, we found that the expression of FSTL3 in trophoblasts were increased under hypoxic culture conditions and that this increased expression is involved in the regulation of trophoblast functions, including cell invasion, migration, lipid storage, and apoptosis (Xie et al, 2018). With regard to the pathogenesis of preeclampsia, the main etiology is the inadequate trophoblast cell invasion into the uterine vessel (Schneyer et al, 2004;Karumanchi and Stillman, 2006).…”

Section: Discussionmentioning

confidence: 79%

GDF8 Promotes the Cell Invasiveness in Human Trophoblasts by Upregulating the Expression of Follistatin-Like 3 Through the ALK5-SMAD2/3 Signaling Pathway

Xie

Zhu

Klausen

et al. 2020

Front. Cell Dev. Biol.

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Growth differentiation factor 8 (GDF8) and its antagonist follistatin-like 3 (FSTL3) are expressed in the placenta during early pregnancy. These two factors may have a role to play in the regulation of normal placentation. However, whether GDF8 can regulate the expression of FSTL3 in human trophoblasts remains to be elucidated. In this study, we aimed to investigate the effects of GDF8 on the expression of FSTL3 and the underlying molecular mechanisms using human trophoblasts as a study model. Our results showed that GDF8 significantly upregulates the expression and production of FSTL3, which further promotes cell invasiveness in immortalized extravillous cytotrophoblast cells and primary extravillous cytotrophoblast cells obtained from human first-trimester placentae. Additionally, using an siRNA-mediated knockdown approach, we found that this regulatory effect is most likely mediated by the ALK5-Sma-and Mad-related protein (SMAD)2/3-induced signaling pathway. These findings deepen our understanding of the functional roles of GDF8 and FSTL3 in the regulation of cell invasiveness of trophoblasts.

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“…ALPP, CYP19A1, and FSTL3 were excluded from further analysis as they have been previously reported to be associated with the pathology of PE or FGR. (13)(14)(15)(16)(17)…”

Section: Resultsmentioning

confidence: 99%

Upregulation of ENDOU in cytotrophoblasts from placenta complicated with preeclampsia and fetal growth restriction

Nomoto

Kotani

Miki

et al. 2021

J. Clin. Biochem. Nutr.

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Placental hypoplasia is associated with the pathophysiology of fetal growth restriction and preeclampsia. The placenta consists of differentiated trophoblasts, including cytotrophoblasts, syncytiotrophoblasts, and extravillous trophoblasts. Cytotrophoblasts are thought to have stem-like characteristics and the ability to differentiate into syncytiotrophoblasts and extravillous trophoblasts. However, it is poorly understood whether isolated cytotrophoblasts derived from hypoplastic placentas have specific features compared with those in normal placentas. This study aimed to determine the features of cytotrophoblasts in hypoplastic placentas. Differentially expressed proteins between isolated cytotrophoblasts from hypoplastic placenta with fetal growth restriction and those from the normal placenta were determined by liquid chromatography-tandem mass spectrometry. Among 6,802 proteins, 1,253 and 2,129 proteins were more than 2-fold upregulated and downregulated, respectively. Among them, ENDOU (endonuclease, poly(U) specific), which has high homology with the coronavirus endoribonuclease nonstructural protein 15 (Nsp15), showed a significantly increased expression in cytotrophoblasts from the placenta with fetal growth restriction related to preeclampsia compared with those in normal control placenta. These results provide insight into the pathological mechanisms of placental hypoplasia and additional information on preeclamptic symptoms in cases of SARS-CoV-2 infected placenta, although further investigation is needed.

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Involvement of follistatin-like 3 in preeclampsia

Cited by 30 publications

References 35 publications

Placental microRNAs in pregnancies with early onset intrauterine growth restriction and preeclampsia: potential impact on gene expression and pathophysiology

Placental microRNAs in pregnancies with early onset intrauterine growth restriction and preeclampsia: potential impact on gene expression and pathophysiology

GDF8 Promotes the Cell Invasiveness in Human Trophoblasts by Upregulating the Expression of Follistatin-Like 3 Through the ALK5-SMAD2/3 Signaling Pathway

Upregulation of ENDOU in cytotrophoblasts from placenta complicated with preeclampsia and fetal growth restriction

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