Elabela and Apelin actions in healthy and pathological pregnancies

Eberlé, Delphine; Marousez, Lucie; Hanssens, Sandy; Knauf, Claude; Breton, Christophe; Deruelle, Philippe; Lésage, Jean

doi:10.1016/j.cytogfr.2019.03.003

Cited by 39 publications

(66 citation statements)

References 85 publications

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“…Many authors have already highlighted an antiapoptotic effect of apelin in various types of cells, especially in human brain cells, indicating the neuroprotective role of this peptide [46,47]. Moreover, apelin protects rat ovarian cells and adrenal cells from cell death [31,48], which is in agreement with our findings.…”

Section: Discussionsupporting

confidence: 93%

“…Thus, we investigated the action of this isoform. So far, the participation of the apelin/APJ system has been studied in the regulation of placenta function, foetal growth, but also in the context of the development and prevention of pregnancy pathologies such as gestational diabetes, preeclampsia or IUGR [37,39,40]. There is substantial evidence of the important role of apelin in pregnancy.…”

Section: Discussionmentioning

confidence: 99%

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Anti-Apoptotic Effect of Apelin in Human Placenta: Studies on BeWo Cells and Villous Explants from Third-Trimester Human Pregnancy

Mlyczyńska

Myszka

Kurowska

et al. 2021

IJMS

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Previously, we demonstrated the expression of apelin and G-protein-coupled receptor APJ in human placenta cell lines as well as its direct action on placenta cell proliferation and endocrinology. The objective of this study was to examine the effect of apelin on placenta apoptosis in BeWo cells and villous explants from the human third trimester of pregnancy. The BeWo cells and villous explants were incubated with apelin (2 and 20 ng/mL) alone or with staurosporine for 24 to 72 h. First, we analysed the dose- and time-dependent effect of apelin on the expression of apoptotic factors on the mRNA level by real-time PCR and on the protein level using Western blot. Next, we checked caspase 3 and 7 activity by Caspase-Glo 3/7, DNA fragmentation by the Cell Death Detection ELISA kit and oxygen consumption by the MitoXpress-Xtra Oxygen Consumption assay. We found that apelin increased the expression of pro-survival and decreased proapoptotic factors on mRNA and protein levels in both BeWo cells and villous explants. Additionally, apelin inhibited caspase 3 and 7 activity and DNA fragmentation in staurosporine-induced apoptosis as also attenuated oxidative stress by increasing extracellular oxygen consumption. The antiapoptotic effect of apelin in BeWo cells was mediated by the APJ receptor and mitogen-activated protein kinase (ERK1/2/MAP3/1) and protein kinase B (AKT). The obtained results showed the antiapoptotic effect of apelin on trophoblast cells, suggesting its participation in the development of the placenta.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Anti-Apoptotic Effect of Apelin in Human Placenta: Studies on BeWo Cells and Villous Explants from Third-Trimester Human Pregnancy

Mlyczyńska

Myszka

Kurowska

et al. 2021

IJMS

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“…The study by Zhou et al used a concentration of ELA that was 20 times higher (5 nmol/L) to assume that this extremely high concentration of ELA used in their study caused an upregulation of APLNR expression and signalling 8 . In addition, Chng et al confirmed that ELA, in concert with the TGF‐β pathway, is involved in endoderm differentiation via maintaining hESCs primed toward the mesendoderm lineage 27,28 . This study further supports this evidence and suggests that ELA can enhance cell viability, migration and tube formation in EC.…”

Section: Discussionsupporting

confidence: 67%

ELABELA improves endothelial cell function via the ELA–APJ axis by activating the PI3K/Akt signalling pathway in HUVECs and EA.hy926 cells

Wang¹,

Liang²,

Guo³

et al. 2020

Clin Exp Pharma Physio

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Destruction of endothelial cells (ECs) function is involved in the structural and functional pathophysiological processes of preeclampsia (PE). Vascular endothelial injury may pre‐exist for several years in women that develop PE and may pose increased risks for hypertension, coronary artery disease, and type‐2 diabetes mellitus. Previous findings showed that Elabela (ELA), the endogenous ligand of the apelin (APJ) receptor expressed mainly on ECs, may play a protective role in early pregnancy and prevent PE. However, the exact functional role and molecular mechanisms of ELA are unclear. Here, we aimed to classify whether and how ELA improves EC function via the ELA–APJ axis. Two human umbilical vein endothelial cell (HUVEC) lines, namely HUVECs and EA.hy926, were treated with ELA, and then their cellular activities were studied by performing CCK‐8 tests, scratch‐wound analysis, and tube‐formation assays. Doses of ELA exceeding 0.01 μmol/L markedly improved the cell viability, migration, and tube formation ability of HUVECs and EA.hy926 cells. Western blot analysis indicated that the above effects caused by ELA were related to upregulation of the APJ receptor and activation of PI3K/Akt signalling. Further verification tests were performed using the PI3K inhibitor wortmannin, and the results illustrated that inhibiting PI3K/Akt signalling blocked the positive effects of ELA on EC function and APJ receptor expression. Taken together, our findings indicate that ELA may alter EC function via the ELA–APJ axis and PI3K/Akt signalling and that ELA shows promise for use in endothelial dysfunction therapy for preventing and treating PE.

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“…Exercise creates a hypoxic environment in the placenta (16), which stimulates vasculogenesis. These developing vascular endothelial cells are major sources of apelin secretion (17). Placental vascularization was increased because of maternal exercise (16).…”

Section: Apelin Supplementation During Pregnancy Promotes Fetal Bat Dmentioning

confidence: 99%

Maternal exercise via exerkine apelin enhances brown adipogenesis and prevents metabolic dysfunction in offspring mice

et al. 2020

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The obesity rate is rapidly increasing, which has been attributed to lack of exercise and excessive energy intake. Here, we found a previously unidentified explanation, due to lack of maternal exercise. In this study, healthy maternal mice were assigned either to a sedentary lifestyle or to exercise daily, and fetal brown adipose tissue (BAT) development and offspring metabolic health were analyzed. Compared to the sedentary group, maternal exercise enhanced DNA demethylation of Prdm16 promoter and BAT development and prevented obesity of offspring when challenged with a high-energy diet. Apelin, an exerkine, was elevated in both maternal and fetal circulations due to exercise, and maternal administration of apelin mimicked the beneficial effects of exercise on fetal BAT development and offspring metabolic health. Together, maternal exercise enhances thermogenesis and the metabolic health of offspring mice, suggesting that the sedentary lifestyle during pregnancy contributes to the obesity epidemic in modern societies.

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Elabela and Apelin actions in healthy and pathological pregnancies

Cited by 39 publications

References 85 publications

Anti-Apoptotic Effect of Apelin in Human Placenta: Studies on BeWo Cells and Villous Explants from Third-Trimester Human Pregnancy

Anti-Apoptotic Effect of Apelin in Human Placenta: Studies on BeWo Cells and Villous Explants from Third-Trimester Human Pregnancy

ELABELA improves endothelial cell function via the ELA–APJ axis by activating the PI3K/Akt signalling pathway in HUVECs and EA.hy926 cells

Maternal exercise via exerkine apelin enhances brown adipogenesis and prevents metabolic dysfunction in offspring mice

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