Sexual dimorphism in PAR 2 -dependent regulation of primitive colonic cells.

Autor: Noguerol J; IRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, CHU Purpan, place du Dr Baylac, 31024 Toulouse Cedex 3, Toulouse, France., Roustan PJ; IRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, CHU Purpan, place du Dr Baylac, 31024 Toulouse Cedex 3, Toulouse, France., N'Taye M; IRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, CHU Purpan, place du Dr Baylac, 31024 Toulouse Cedex 3, Toulouse, France., Delcombel L; IRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, CHU Purpan, place du Dr Baylac, 31024 Toulouse Cedex 3, Toulouse, France., Rolland C; IRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, CHU Purpan, place du Dr Baylac, 31024 Toulouse Cedex 3, Toulouse, France., Guiraud L; IRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, CHU Purpan, place du Dr Baylac, 31024 Toulouse Cedex 3, Toulouse, France., Sagnat D; IRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, CHU Purpan, place du Dr Baylac, 31024 Toulouse Cedex 3, Toulouse, France., Edir A; IRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, CHU Purpan, place du Dr Baylac, 31024 Toulouse Cedex 3, Toulouse, France., Bonnart C; IRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, CHU Purpan, place du Dr Baylac, 31024 Toulouse Cedex 3, Toulouse, France., Denadai-Souza A; IRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, CHU Purpan, place du Dr Baylac, 31024 Toulouse Cedex 3, Toulouse, France., Deraison C; IRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, CHU Purpan, place du Dr Baylac, 31024 Toulouse Cedex 3, Toulouse, France., Vergnolle N; IRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, CHU Purpan, place du Dr Baylac, 31024 Toulouse Cedex 3, Toulouse, France., Racaud-Sultan C; IRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, CHU Purpan, place du Dr Baylac, 31024 Toulouse Cedex 3, Toulouse, France. claire.racaud@inserm.fr.
Jazyk: angličtina
Zdroj: Biology of sex differences [Biol Sex Differ] 2019 Sep 06; Vol. 10 (1), pp. 47. Date of Electronic Publication: 2019 Sep 06.
DOI: 10.1186/s13293-019-0262-6
Abstrakt: 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.
Databáze: MEDLINE
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