Régulation des fonctions des myofibroblastes portaux par le stress du réticulum endoplasmique

Emilien Loeuillard 1
1 Inserm UMR_S 938 - Pathologies biliaires, fibrose et cancer du foie
CHU Saint-Antoine [APHP], CR Saint-Antoine - Centre de Recherche Saint-Antoine
Abstract : Hepatic fibrosis is the consequence of all chronic liver diseases and is characterized by an abnormal extra cellular matrix deposition by myofibroblasts. Portal myofibroblasts (PMF), a subpopulation of hepatic myofibroblasts, play a major role in fibrosis progression and angiogenesis. Accumulating evidences indicate an important role of endoplasmic reticulum (ER) stress in hepatic fibrosis. The aims of this study were to determine whether an ER stress occured in PMF during fibrosis and affected the functions of these cells, and to study the effect of the molecular chaperone TUDCA used in biliary diseases, on ER stress. The phenotype of in vivo activated-PMF obtained from rat fibrotic liver after cholestasis was compared with the phenotype of control PMF that we previously characterized. Our results showed that in vivo activated-PMF underwent ER stress with PERK pathway activation. This ER stress had no effect on myofibroblastic differentiation but reduced PMF proliferation and migration and increased PMF angiogenesis capacity. TUDCA had no effect on these parameters. In conclusion, PMF display ER stress during their activation. ER stress stimulates their pro-angiogenic proprieties and thereby may promote fibrosis progression. However, ER stress also inhibits their proliferation and migration functions, and thereby could provide a negative control loop to restrict their expansion.
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Emilien Loeuillard. Régulation des fonctions des myofibroblastes portaux par le stress du réticulum endoplasmique. Physiologie [q-bio.TO]. Université Pierre et Marie Curie - Paris VI, 2017. Français. ⟨NNT : 2017PA066071⟩. ⟨tel-02022475v2⟩

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