Sexual dimorphism in PAR2-dependent regulation of primitive colonic cells

Autor: 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
Přispěvatelé: Institut de Recherche en Santé Digestive (IRSD ), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Fond Unique Interministeriel (FUI) program by the Région Midi-Pyrénées, the Banque Publique d’Investissement (BPI) de France, Fonds Européens de Développement Régional (FEDER), (ANR-11-EQPX-0003), ANR-11-EQPX-0003,ANINFIMIP,Equipements plateforme animalerie infectieuse de haute-sécurité de Midi Pyrénées(2011), European Project: 310973,EC:FP7:ERC,ERC-2012-StG_20111109,PIPE(2013), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Racaud-Sultan, Claire, Equipements plateforme animalerie infectieuse de haute-sécurité de Midi Pyrénées - - ANINFIMIP2011 - ANR-11-EQPX-0003 - EQPX - VALID, Physiology of the Intestine: Proteases from the Epithelium - PIPE - - EC:FP7:ERC2013-04-01 - 2018-03-31 - 310973 - VALID, Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT)
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: Biology of Sex Differences
Biology of Sex Differences, 2019, 10 (1), pp.47. ⟨10.1186/s13293-019-0262-6⟩
Biology of Sex Differences, BioMed Central, 2019, 10 (1), pp.47. ⟨10.1186/s13293-019-0262-6⟩
Biology of Sex Differences, BioMed Central, 2019, 10, pp.47. ⟨10.1186/s13293-019-0262-6⟩
Biology of Sex Differences, Vol 10, Iss 1, Pp 1-15 (2019)
Biology of Sex Differences 1 (10), 3-15. (2019)
ISSN: 2042-6410
DOI: 10.1186/s13293-019-0262-6⟩
Popis: 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 PAR2 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 PAR2 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. PAR2 activation was triggered by the addition of SLIGRL agonist peptide in the culture medium. PAR2-deficient mice were used to study the impact of PAR2 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 PAR2 activation by specific PAR2 agonist peptide. The proliferation of male epithelial cells was lower compared to females but was specifically increased in PAR2 knockout male cells. PAR2 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 PAR2-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 PAR2-dependent regulation of primitive cells of the colon crypt. ispartof: BIOLOGY OF SEX DIFFERENCES vol:10 issue:1 ispartof: location:England status: published
Databáze: OpenAIRE
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