Losartan impairs HTR-8/SVneo trophoblast migration through inhibition of angiotensin II-induced pro-inflammatory profile in human endometrial stromal cells
Copyright © 2023 Elsevier Inc. All rights reserved..
A deep interaction between the endometrium and the invading trophoblast occurs during implantation in humans, with the acquisition of uterine receptivity to the invading embryo promoted by an elevation of pro-inflammatory cytokines in the endometrium, and the invasiveness of decidualizing endometrial stromal cells, augmented by trophoblast-derived signals. Considering that usage of angiotensin II type 1 (AT1) receptor blockers, among other renin-angiotensin system (RAS) antagonists, is associated with adverse pregnancy outcomes, here we aim to analyse the involvement of AT1 receptor in the reciprocal dialogue occurring between endometrial stroma and trophoblast cells. In human endometrial stromal cells (T-HESC) pre-incubated with a decidualization cocktail, angiotensin (Ang) II increased protein expression of prolactin and FOXO1, markers of endometrial decidualization, while promoting nuclear translocation of FOXO1. In addition, Ang II treatment increased CXCL8, and matrix metalloprotease (MMP)-2 levels in T-HESC. Incubation with the AT1 receptor blocker losartan or with an NFAT signalling inhibitor, decreased Ang II-induced secretion of prolactin, CXCL8, and MMP-2 in T-HESC. In a wound healing assay, conditioned medium (CM) obtained from Ang II-treated T-HESC, but not CM from losartan-pre-incubated T-HESC, increased migration of HTR-8/SVneo trophoblasts, effect that was inhibited in the presence of a CXCL8-neutralizing antibody. An increased secretion of CXCL8 and MMP-2 was observed after treatment of T-HESC with CM obtained from HTR-8/SVneo cells, which was not observed in T-HESC pre-incubated with losartan or with the NFAT inhibitor. This study evidenced a reciprocal RAS-coded messaging between trophoblast and ESC which is affected by the AT1 receptor blocker losartan.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:461 |
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| Enthalten in: |
Toxicology and applied pharmacology - 461(2023) vom: 15. Feb., Seite 116383 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Macchi, Rosario [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 15.02.2023 Date Revised 20.03.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.taap.2023.116383 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM351933026 |
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| 245 | 1 | 0 | |a Losartan impairs HTR-8/SVneo trophoblast migration through inhibition of angiotensin II-induced pro-inflammatory profile in human endometrial stromal cells |
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| 520 | |a A deep interaction between the endometrium and the invading trophoblast occurs during implantation in humans, with the acquisition of uterine receptivity to the invading embryo promoted by an elevation of pro-inflammatory cytokines in the endometrium, and the invasiveness of decidualizing endometrial stromal cells, augmented by trophoblast-derived signals. Considering that usage of angiotensin II type 1 (AT1) receptor blockers, among other renin-angiotensin system (RAS) antagonists, is associated with adverse pregnancy outcomes, here we aim to analyse the involvement of AT1 receptor in the reciprocal dialogue occurring between endometrial stroma and trophoblast cells. In human endometrial stromal cells (T-HESC) pre-incubated with a decidualization cocktail, angiotensin (Ang) II increased protein expression of prolactin and FOXO1, markers of endometrial decidualization, while promoting nuclear translocation of FOXO1. In addition, Ang II treatment increased CXCL8, and matrix metalloprotease (MMP)-2 levels in T-HESC. Incubation with the AT1 receptor blocker losartan or with an NFAT signalling inhibitor, decreased Ang II-induced secretion of prolactin, CXCL8, and MMP-2 in T-HESC. In a wound healing assay, conditioned medium (CM) obtained from Ang II-treated T-HESC, but not CM from losartan-pre-incubated T-HESC, increased migration of HTR-8/SVneo trophoblasts, effect that was inhibited in the presence of a CXCL8-neutralizing antibody. An increased secretion of CXCL8 and MMP-2 was observed after treatment of T-HESC with CM obtained from HTR-8/SVneo cells, which was not observed in T-HESC pre-incubated with losartan or with the NFAT inhibitor. This study evidenced a reciprocal RAS-coded messaging between trophoblast and ESC which is affected by the AT1 receptor blocker losartan | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a Angiotensin II type 1 receptor | |
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| 650 | 4 | |a Endometrial stromal cells | |
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| 650 | 4 | |a Trophoblast migration | |
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| 700 | 1 | |a Parrado, Andrea C |e verfasserin |4 aut | |
| 700 | 1 | |a Salaverry, Luciana S |e verfasserin |4 aut | |
| 700 | 1 | |a Blanco, Guillermo A |e verfasserin |4 aut | |
| 700 | 1 | |a Castro, Marisa S |e verfasserin |4 aut | |
| 700 | 1 | |a Rey-Roldán, Estela B |e verfasserin |4 aut | |
| 700 | 1 | |a Canellada, Andrea M |e verfasserin |4 aut | |
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