Cargando…
Sexual dimorphism in PAR(2)-dependent regulation of primitive colonic cells
BACKGROUND: Sexual dimorphism in biological responses is a critical knowledge for therapeutic proposals. However, gender differences in intestinal stem cell physiology have been poorly studied. Given the important role of the protease-activated receptor PAR(2) in the control of colon epithelial prim...
Autores principales: | , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6731565/ https://www.ncbi.nlm.nih.gov/pubmed/31492202 http://dx.doi.org/10.1186/s13293-019-0262-6 |
_version_ | 1783449694207213568 |
---|---|
author | Noguerol, Julie Roustan, Pierre-Jean N’Taye, Mikael Delcombel, Léo Rolland, Corinne Guiraud, Laura Sagnat, David Edir, Anissa Bonnart, Chrystelle Denadai-Souza, Alexandre Deraison, Céline Vergnolle, Nathalie Racaud-Sultan, Claire |
author_facet | Noguerol, Julie Roustan, Pierre-Jean N’Taye, Mikael Delcombel, Léo Rolland, Corinne Guiraud, Laura Sagnat, David Edir, Anissa Bonnart, Chrystelle Denadai-Souza, Alexandre Deraison, Céline Vergnolle, Nathalie Racaud-Sultan, Claire |
author_sort | Noguerol, Julie |
collection | PubMed |
description | BACKGROUND: Sexual dimorphism in biological responses is a critical knowledge for therapeutic proposals. However, gender differences in intestinal stem cell physiology have been poorly studied. Given the important role of the protease-activated receptor PAR(2) in the control of colon epithelial primitive cells and cell cycle genes, we have performed a sex-based comparison of its expression and of the effects of PAR(2) activation or knockout on cell proliferation and survival functions. METHODS: Epithelial primitive cells isolated from colons from male and female mice were cultured as colonoids, and their number and size were measured. PAR(2) activation was triggered by the addition of SLIGRL agonist peptide in the culture medium. PAR(2)-deficient mice were used to study the impact of PAR(2) expression on colon epithelial cell culture and gene expression. RESULTS: Colonoids from female mice were more abundant and larger compared to males, and these differences were further increased after PAR(2) activation by specific PAR(2) agonist peptide. The proliferation of male epithelial cells was lower compared to females but was specifically increased in PAR(2) knockout male cells. PAR(2) expression was higher in male colon cells compared to females and controlled the gene expression and activation of key negative signals of the primitive cell proliferation. This PAR(2)-dependent brake on the proliferation of male colon primitive cells was correlated with stress resistance. CONCLUSIONS: Altogether, these data demonstrate that there is a sexual dimorphism in the PAR(2)-dependent regulation of primitive cells of the colon crypt. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13293-019-0262-6) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6731565 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-67315652019-09-12 Sexual dimorphism in PAR(2)-dependent regulation of primitive colonic cells Noguerol, Julie Roustan, Pierre-Jean N’Taye, Mikael Delcombel, Léo Rolland, Corinne Guiraud, Laura Sagnat, David Edir, Anissa Bonnart, Chrystelle Denadai-Souza, Alexandre Deraison, Céline Vergnolle, Nathalie Racaud-Sultan, Claire Biol Sex Differ Research BACKGROUND: Sexual dimorphism in biological responses is a critical knowledge for therapeutic proposals. However, gender differences in intestinal stem cell physiology have been poorly studied. Given the important role of the protease-activated receptor PAR(2) in the control of colon epithelial primitive cells and cell cycle genes, we have performed a sex-based comparison of its expression and of the effects of PAR(2) activation or knockout on cell proliferation and survival functions. METHODS: Epithelial primitive cells isolated from colons from male and female mice were cultured as colonoids, and their number and size were measured. PAR(2) activation was triggered by the addition of SLIGRL agonist peptide in the culture medium. PAR(2)-deficient mice were used to study the impact of PAR(2) expression on colon epithelial cell culture and gene expression. RESULTS: Colonoids from female mice were more abundant and larger compared to males, and these differences were further increased after PAR(2) activation by specific PAR(2) agonist peptide. The proliferation of male epithelial cells was lower compared to females but was specifically increased in PAR(2) knockout male cells. PAR(2) expression was higher in male colon cells compared to females and controlled the gene expression and activation of key negative signals of the primitive cell proliferation. This PAR(2)-dependent brake on the proliferation of male colon primitive cells was correlated with stress resistance. CONCLUSIONS: Altogether, these data demonstrate that there is a sexual dimorphism in the PAR(2)-dependent regulation of primitive cells of the colon crypt. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13293-019-0262-6) contains supplementary material, which is available to authorized users. BioMed Central 2019-09-06 /pmc/articles/PMC6731565/ /pubmed/31492202 http://dx.doi.org/10.1186/s13293-019-0262-6 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Noguerol, Julie Roustan, Pierre-Jean N’Taye, Mikael Delcombel, Léo Rolland, Corinne Guiraud, Laura Sagnat, David Edir, Anissa Bonnart, Chrystelle Denadai-Souza, Alexandre Deraison, Céline Vergnolle, Nathalie Racaud-Sultan, Claire Sexual dimorphism in PAR(2)-dependent regulation of primitive colonic cells |
title | Sexual dimorphism in PAR(2)-dependent regulation of primitive colonic cells |
title_full | Sexual dimorphism in PAR(2)-dependent regulation of primitive colonic cells |
title_fullStr | Sexual dimorphism in PAR(2)-dependent regulation of primitive colonic cells |
title_full_unstemmed | Sexual dimorphism in PAR(2)-dependent regulation of primitive colonic cells |
title_short | Sexual dimorphism in PAR(2)-dependent regulation of primitive colonic cells |
title_sort | sexual dimorphism in par(2)-dependent regulation of primitive colonic cells |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6731565/ https://www.ncbi.nlm.nih.gov/pubmed/31492202 http://dx.doi.org/10.1186/s13293-019-0262-6 |
work_keys_str_mv | AT nogueroljulie sexualdimorphisminpar2dependentregulationofprimitivecoloniccells AT roustanpierrejean sexualdimorphisminpar2dependentregulationofprimitivecoloniccells AT ntayemikael sexualdimorphisminpar2dependentregulationofprimitivecoloniccells AT delcombelleo sexualdimorphisminpar2dependentregulationofprimitivecoloniccells AT rollandcorinne sexualdimorphisminpar2dependentregulationofprimitivecoloniccells AT guiraudlaura sexualdimorphisminpar2dependentregulationofprimitivecoloniccells AT sagnatdavid sexualdimorphisminpar2dependentregulationofprimitivecoloniccells AT ediranissa sexualdimorphisminpar2dependentregulationofprimitivecoloniccells AT bonnartchrystelle sexualdimorphisminpar2dependentregulationofprimitivecoloniccells AT denadaisouzaalexandre sexualdimorphisminpar2dependentregulationofprimitivecoloniccells AT deraisonceline sexualdimorphisminpar2dependentregulationofprimitivecoloniccells AT vergnollenathalie sexualdimorphisminpar2dependentregulationofprimitivecoloniccells AT racaudsultanclaire sexualdimorphisminpar2dependentregulationofprimitivecoloniccells |