Molecular insights of cholestasis in MDR2KO murine liver organoids. A model for the early detection of cirrhosis and HCC

ABSTRACT: MDR3 (multidrug resistance 3) deficiency in humans (MDR2 in mice) causes progressive familial intrahepatic cholestasis type 3 (PFIC3). PFIC3 is a lethal disease characterized by an early onset of intrahepatic cholestasis, progressing to liver cirrhosis which is considered a preneoplastic condition, at risk of hepatocellular carcinoma (HCC). MDR3 is a phosphatidylcholine transporter at the canalicular membrane of hepatocytes. Hepatocyte-like organoids from MDR2-deficient mice (MDR2KO) were used in this work to study the molecular alterations caused by the deficiency of this transporter. Proteomic analysis by mass spectrometry allowed characterization of 279 proteins that were differentially expressed in MDR2KO compared to WT organoids. Functional enrichment analysis indicated alterations in three main cellular functions: (1) interaction with the extracellular matrix, (2) remodeling intermediary metabolism, (3) cell proliferation and differentiation. The affected cellular processes were validated by orthogonal molecular biology techniques such as qPCR and Western blot. Our results point to molecular mechanisms associated with PFIC3 that may drive the progression to liver cirrhosis and HCC and suggest proteins and cellular processes that could support the development of early detection strategies for these severe liver diseases.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): 3-d Shape

DISEASE(S): Progressive Familial Intrahepatic Cholestasis 3

SUBMITTER: Irene Blázquez García  

LAB HEAD: Fernando J. Corrales

PROVIDER: PXD047995 | Pride | 2026-09-17

REPOSITORIES: Pride