RIPK1 in Liver Parenchymal Cells Limits Murine Hepatitis during Acute CCl4-Induced Liver Injury - Université de Rennes Accéder directement au contenu
Article Dans Une Revue International Journal of Molecular Sciences Année : 2022

RIPK1 in Liver Parenchymal Cells Limits Murine Hepatitis during Acute CCl4-Induced Liver Injury

Résumé

Some life-threatening acute hepatitis originates from drug-induced liver injury (DILI). Carbon tetrachloride (CCl4)-induced acute liver injury in mice is the widely used model of choice to study acute DILI, which pathogenesis involves a complex interplay of oxidative stress, necrosis, and apoptosis. Since the receptor interacting protein kinase-1 (RIPK1) is able to direct cell fate towards survival or death, it may potentially affect the pathological process of xenobiotic-induced liver damage. Two different mouse lines, either deficient for Ripk1 specifically in liver parenchymal cells (Ripk1(LPC-KO)) or for the kinase activity of RIPK1 (Ripk1(K45A), kinase dead), plus their respective wild-type littermates (Ripk1(fl/fl), Ripk1(wt/wt)), were exposed to single toxic doses of CCl4. This exposure led in similar injury in Ripk1(K45A) mice and their littermate controls. However, Ripk1(LPC-KO) mice developed more severe symptoms with massive hepatocyte apoptosis as compared to their littermate controls. A pretreatment with a TNF-alpha receptor decoy exacerbated liver apoptosis in both Ripk1(fl/fl) and Ripk1(LPC-KO) mice. Besides, a FasL antagonist promoted hepatocyte apoptosis in Ripk1(fl/fl) mice but reduced it in Ripk1(LPC-KO) mice. Thus, the scaffolding properties of RIPK1 protect hepatocytes from apoptosis during CCl4 intoxication. TNF-alpha and FasL emerged as factors promoting hepatocyte survival. These protective effects appeared to be independent of RIPK1, at least in part, for TNF-alpha, but dependent on RIPK1 for FasL. These new data complete the deciphering of the molecular mechanisms involved in DILI in the context of research on their prevention or cure.
Fichier principal
Vignette du fichier
ijms-23-07367-v2.pdf (11.27 Mo) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte

Dates et versions

hal-03763566 , version 1 (29-08-2022)

Licence

Paternité

Identifiants

Citer

Huma Hameed, Muhammad Farooq Ahmad, Céline Vuillier, Claire Piquet-Pellorce, Annaïg Hamon, et al.. RIPK1 in Liver Parenchymal Cells Limits Murine Hepatitis during Acute CCl4-Induced Liver Injury. International Journal of Molecular Sciences, 2022, 23 (13), pp.7367. ⟨10.3390/ijms23137367⟩. ⟨hal-03763566⟩
36 Consultations
14 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More