Decidualisation of human endometrial stromal cells is associated with increased expression and secretion of prorenin

Lumbers, Eugenie R., Wang, Yu, Delforce, Sarah J., Corbisier de Meaultsart, Celine, Logan, Philip C., Mitchell, Murray D. and Pringle, Kirsty G. (2015) Decidualisation of human endometrial stromal cells is associated with increased expression and secretion of prorenin. Reproductive Biology and Endocrinology, 13 129: . doi:10.1186/s12958-015-0127-8


Author Lumbers, Eugenie R.
Wang, Yu
Delforce, Sarah J.
Corbisier de Meaultsart, Celine
Logan, Philip C.
Mitchell, Murray D.
Pringle, Kirsty G.
Title Decidualisation of human endometrial stromal cells is associated with increased expression and secretion of prorenin
Journal name Reproductive Biology and Endocrinology   Check publisher's open access policy
ISSN 1477-7827
Publication date 2015-11-25
Year available 2015
Sub-type Article (original research)
DOI 10.1186/s12958-015-0127-8
Open Access Status DOI
Volume 13
Issue 129
Total pages 9
Place of publication London, United Kingdom
Publisher BioMed Central
Language eng
Formatted abstract
Background
In pregnancy, the decidualised endometrium expresses high levels of prorenin and other genes of the renin-angiotensin system (RAS) pathway. In this study we aimed to determined if the RAS was present in endometrial stromal cells and if decidualisation upregulated the expression of prorenin, the prorenin receptor ((P)RR) and associated RAS pathways. Immortalised human endometrial stromal cells (HESCs) can be stimulated to decidualise by combined treatment with medroxyprogesterone acetate (MPA), 17β-estradiol (E2) and cAMP (MPA-mix) or with 5-aza-2’-deoxycytidine (AZA), a global demethylating agent.

Methods
HESCs were incubated for 10 days with one of the following treatments: vehicle, MPA-mix, a combination of medroxyprogesterone acetate (MPA) and estradiol-17β alone, or AZA. Messenger RNA abundance and protein levels of prorenin (REN), the (P)RR (ATP6AP2), angiotensinogen (AGT), angiotensin converting enzyme (ACE), angiotensin II type 1 receptor (AGTR1), vascular endothelial growth factor (VEGF), and plasminogen activator inhibitor-1 (PAI-1) were measured by real-time PCR and ELISA’s, respectively. Promyelocytic zinc finger (PLZF) and phospho-inositol-3 kinase (PIK3R1) mRNA abundances were also measured.

Results
HESCs expressed the prorenin receptor (ATP6AP2), REN, AGT, ACE and low levels of AGTR1. MPA-mix and AZA stimulated expression of REN. Prorenin protein secretion was increased in MPA-mix treated HESCs. E 2  + MPA had no effect on any RAS genes. MPA-mix treatment was associated with increased VEGF (VEGFA) and PAI-1 (SERPINE1) mRNA and VEGF protein.

Conclusions
An endometrial prorenin receptor/renin angiotensin system is activated by decidualisation. Since (P)RR is abundant, the increase in prorenin secretion could have stimulated VEGF A and SERPINE1 expression via Ang II, as both ACE and AGTR1 are present, or by Ang II independent pathways. Activation of the RAS in human endometrium with decidualisation, through stimulation of VEGF expression and secretion, could be critical in establishing an adequate blood supply to the developing maternal placental vascular bed.
Keyword Prorenin
ATP6AP2
Angiotensinogen
Decidualisation
5-aza-2'deoxycytidine
Angiotensin
VEGF
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
Official 2016 Collection
 
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