mPRα and PR co-operate in progesterone inhibition of endothelial cell focal adhesion

in Journal of Molecular Endocrinology
Authors:
Yefei PangMarine Science Institute, University of Texas at Austin, Port Aransas, Texas, USA

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https://orcid.org/0000-0003-1773-1697
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Peter ThomasMarine Science Institute, University of Texas at Austin, Port Aransas, Texas, USA

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Correspondence should be addressed to Y Pang or P Thomas: yfpang@utexas.edu or peter.thomas@utexas.edu
DOI:
https://doi.org/10.1530/JME-22-0073
Volume/Issue:
Volume 70: Issue 1
Article Type:
Research Article
Article ID:
e220073
Online Publication Date:
07 Dec 2022
Copyright:
© Society for Endocrinology 2022
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Progesterone causes vascular smooth muscle cell relaxation through membrane progesterone receptors (mPRs), which are members of the progestin and adipoQ receptor (PAQR) family, and nuclear PRs (nPRs). However, beneficial vascular effects of progesterone in preventing pre-atherosclerosis and the involvement of mPRs and nPRs remain unclear. The results show short- to long-term treatments with 100 nM progesterone (P4) and specific agonists for mPRs, OD 02-0, and nPRs, R5020, inhibited pre-atherosclerotic events in human umbilical vein endothelial cells (HUVECs), decreasing focal adhesion (FA) by monocytes, FA signaling, HUVEC migration and invasion, and vinculin expression. Progesterone and OD 02-0, but not R5020, inhibited phosphorylation of Src and focal adhesion kinase, critical kinases of FA signaling, within 20 min and migration and invasion of HUVECs and monocyte adhesion after 3 h. These inhibitory P4 and 02-0 effects were attenuated with MAP kinase and Pi3k inhibitors, indicating involvement of these kinases in this mPR-mediated action. However, after 16 h, OD 02-0 was no longer effective in inhibiting FA signaling, while both progesterone and R5020 decreased the activity of the two kinases. Knockdown of receptor expression with siRNA confirmed that mPRα mediates short-term and nPR long-term inhibitory effects of progesterone on FA signaling. Thus, progesterone inhibition of FA signaling and pre-atherosclerosis is coordinated through mPRα and nPRs.

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Print ISSN:
0952-5041
Online ISSN:
1479-6813
Copyright:
© Society for Endocrinology 2022
Article ID:
e220073
Article Type:
Research Article
Received Date:
08 Sep 2022
Accepted Date:
13 Sep 2022
Print Publication Date:
01 Jan 2023
Online Publication Date:
07 Dec 2022
Keywords:
vascular endothelial cells; progesterone; focal adhesion signaling; membrane progesterone receptor alpha (mPRα); nuclear progesterone receptor (nPR); pre-atherosclerosis

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