SUCNR1 Is Expressed in Human Placenta and Mediates Angiogenesis: Significance in Gestational Diabetes.
Adult
Case-Control Studies
Cells, Cultured
Diabetes, Gestational
/ genetics
Endothelium, Vascular
/ metabolism
Female
Human Umbilical Vein Endothelial Cells
Humans
Neovascularization, Pathologic
/ genetics
Neovascularization, Physiologic
/ genetics
Placenta
/ blood supply
Pregnancy
Receptors, G-Protein-Coupled
/ genetics
GDM
SUCNR1
angiogenesis
endothelial cells
placenta
succinate
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
07 Nov 2021
07 Nov 2021
Historique:
received:
10
10
2021
revised:
02
11
2021
accepted:
04
11
2021
entrez:
13
11
2021
pubmed:
14
11
2021
medline:
20
1
2022
Statut:
epublish
Résumé
Placental hypervascularization has been reported in pregnancy-related pathologies such as gestational diabetes mellitus (GDM). Nevertheless, the underlying causes behind this abnormality are not well understood. In this study, we addressed the expression of SUCNR1 (cognate succinate receptor) in human placental endothelial cells and hypothesized that the succinate-SUCNR1 axis might play a role in the placental hypervascularization reported in GDM. We measured significantly higher succinate levels in placental tissue lysates from women with GDM relative to matched controls. In parallel, SUCNR1 protein expression was upregulated in GDM tissue lysates as well as in isolated diabetic fetoplacental arterial endothelial cells (FpECAds). A positive correlation of SUCNR1 and vascular endothelial growth factor (VEGF) protein levels in tissue lysates indicated a potential link between the succinate-SUCNR1 axis and placental angiogenesis. In our in vitro experiments, succinate prompted hallmarks of angiogenesis in human umbilical vein endothelial cells (HUVECs) such as proliferation, migration and spheroid sprouting. These results were further validated in fetoplacental arterial endothelial cells (FpECAs), where succinate induced endothelial tube formation. VEGF gene expression was increased in response to succinate in both HUVECs and FpECAs. Yet, knockdown of SUCNR1 in HUVECs led to suppression of VEGF gene expression and abrogated the migratory ability and wound healing in response to succinate. In conclusion, our data underline SUCNR1 as a promising metabolic target in human placenta and as a potential driver of enhanced placental angiogenesis in GDM.
Identifiants
pubmed: 34769478
pii: ijms222112048
doi: 10.3390/ijms222112048
pmc: PMC8585094
pii:
doi:
Substances chimiques
Receptors, G-Protein-Coupled
0
SUCNR1 protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Austrian Science Fund FWF
ID : DOC 31
Pays : Austria
Organisme : Austrian Science Fund FWF
ID : J 4547
Pays : Austria
Organisme : Austrian Science Fund FWF
ID : W 1226
Pays : Austria
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