Thrombin modifies growth, proliferation and apoptosis of human colon organoids: a protease-activated receptor 1- and protease-activated receptor 4-dependent mechanism - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue British Journal of Pharmacology Année : 2018

Thrombin modifies growth, proliferation and apoptosis of human colon organoids: a protease-activated receptor 1- and protease-activated receptor 4-dependent mechanism

Résumé

Experimental Approach: Crypts were isolated from human colonic resections and cultured for 6 days, forming human colon organoids. Cultured organoids were exposed to 10 and 50 mU·mL−1 of thrombin, in the presence or not of protease‐activated receptor (PAR) antagonists. Organoid morphology, metabolism, proliferation and apoptosis were followed. Key Results: Thrombin favoured organoid maturation leading to a decreased number of immature cystic structures and a concomitant increased number of larger structures releasing cell debris and apoptotic cells. The size of budding structures, metabolic activity and proliferation were significantly reduced in organoid cultures exposed to thrombin, while apoptosis was dramatically increased. Both PAR1 and PAR4 antagonists inhibited apoptosis regardless of thrombin doses. Thrombin‐induced inhibition of proliferation and metabolic activity were reversed by PAR4 antagonist for thrombin's lowest dose and by PAR1 antagonist for thrombin's highest dose. Conclusions and Implications: Overall, our data suggest that the presence of thrombin in the vicinity of human colon epithelial cells favours their maturation at the expense of their regenerative capacities. Our data point to thrombin and its two receptors PAR1 and PAR4 as potential molecular targets for epithelial repair therapies.
Fichier principal
Vignette du fichier
BPH-175-3656.pdf (870.29 Ko) Télécharger le fichier
Origine : Publication financée par une institution
Loading...

Dates et versions

hal-02332340 , version 1 (24-10-2019)

Identifiants

Citer

Morgane Sébert, Alexandre Denadai-Souza, Muriel Quaranta, Claire Racaud-Sultan, Sophie Chabot, et al.. Thrombin modifies growth, proliferation and apoptosis of human colon organoids: a protease-activated receptor 1- and protease-activated receptor 4-dependent mechanism. British Journal of Pharmacology, 2018, 175 (18), pp.3656-3668. ⟨10.1111/bph.14430⟩. ⟨hal-02332340⟩
32 Consultations
60 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More