SUCNR1 Is Expressed in Human Placenta and Mediates Angiogenesis: Significance in Gestational Diabetes

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 hum...

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Autores principales:	Reham Atallah, Juergen Gindlhuber, Wolfgang Platzer, Thomas Bärnthaler, Eva Tatzl, Wolfgang Toller, Jasmin Strutz, Sonja Rittchen, Petra Luschnig, Ruth Birner-Gruenberger, Christian Wadsack, Akos Heinemann
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	succinate SUCNR1 GDM placenta endothelial cells angiogenesis Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/5403c9aba6484bc192cbe749409a9c8c
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spelling	oai:doaj.org-article:5403c9aba6484bc192cbe749409a9c8c2021-11-11T17:26:46ZSUCNR1 Is Expressed in Human Placenta and Mediates Angiogenesis: Significance in Gestational Diabetes10.3390/ijms2221120481422-00671661-6596https://doaj.org/article/5403c9aba6484bc192cbe749409a9c8c2021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/12048https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Placental 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.Reham AtallahJuergen GindlhuberWolfgang PlatzerThomas BärnthalerEva TatzlWolfgang TollerJasmin StrutzSonja RittchenPetra LuschnigRuth Birner-GruenbergerChristian WadsackAkos HeinemannMDPI AGarticlesuccinateSUCNR1GDMplacentaendothelial cellsangiogenesisBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12048, p 12048 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	succinate SUCNR1 GDM placenta endothelial cells angiogenesis Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	succinate SUCNR1 GDM placenta endothelial cells angiogenesis Biology (General) QH301-705.5 Chemistry QD1-999 Reham Atallah Juergen Gindlhuber Wolfgang Platzer Thomas Bärnthaler Eva Tatzl Wolfgang Toller Jasmin Strutz Sonja Rittchen Petra Luschnig Ruth Birner-Gruenberger Christian Wadsack Akos Heinemann SUCNR1 Is Expressed in Human Placenta and Mediates Angiogenesis: Significance in Gestational Diabetes
description	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.
format	article
author	Reham Atallah Juergen Gindlhuber Wolfgang Platzer Thomas Bärnthaler Eva Tatzl Wolfgang Toller Jasmin Strutz Sonja Rittchen Petra Luschnig Ruth Birner-Gruenberger Christian Wadsack Akos Heinemann
author_facet	Reham Atallah Juergen Gindlhuber Wolfgang Platzer Thomas Bärnthaler Eva Tatzl Wolfgang Toller Jasmin Strutz Sonja Rittchen Petra Luschnig Ruth Birner-Gruenberger Christian Wadsack Akos Heinemann
author_sort	Reham Atallah
title	SUCNR1 Is Expressed in Human Placenta and Mediates Angiogenesis: Significance in Gestational Diabetes
title_short	SUCNR1 Is Expressed in Human Placenta and Mediates Angiogenesis: Significance in Gestational Diabetes
title_full	SUCNR1 Is Expressed in Human Placenta and Mediates Angiogenesis: Significance in Gestational Diabetes
title_fullStr	SUCNR1 Is Expressed in Human Placenta and Mediates Angiogenesis: Significance in Gestational Diabetes
title_full_unstemmed	SUCNR1 Is Expressed in Human Placenta and Mediates Angiogenesis: Significance in Gestational Diabetes
title_sort	sucnr1 is expressed in human placenta and mediates angiogenesis: significance in gestational diabetes
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/5403c9aba6484bc192cbe749409a9c8c
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SUCNR1 Is Expressed in Human Placenta and Mediates Angiogenesis: Significance in Gestational Diabetes

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