Your browser doesn't support javascript.
loading
Molecular Insights of Cholestasis in MDR2 Knockout Murine Liver Organoids.
Blázquez-García, Irene; Guerrero, Laura; Cacho-Navas, Cristina; Djouder, Nabil; Millan, Jaime; Paradela, Alberto; Carmona-Rodríguez, Lorena; Corrales, Fernando J.
Afiliação
  • Blázquez-García I; Functional Proteomics Laboratory, Centro Nacional de Biotecnología (CSIC), Madrid 28049, Spain.
  • Guerrero L; Functional Proteomics Laboratory, Centro Nacional de Biotecnología (CSIC), Madrid 28049, Spain.
  • Cacho-Navas C; Centro de Biología Molecular Severo Ochoa (CBMSO), Madrid 28049, Spain.
  • Djouder N; Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid 28029, Spain.
  • Millan J; Centro de Biología Molecular Severo Ochoa (CBMSO), Madrid 28049, Spain.
  • Paradela A; Functional Proteomics Laboratory, Centro Nacional de Biotecnología (CSIC), Madrid 28049, Spain.
  • Carmona-Rodríguez L; Functional Proteomics Laboratory, Centro Nacional de Biotecnología (CSIC), Madrid 28049, Spain.
  • Corrales FJ; Functional Proteomics Laboratory, Centro Nacional de Biotecnología (CSIC), Madrid 28049, Spain.
J Proteome Res ; 23(4): 1433-1442, 2024 04 05.
Article em En | MEDLINE | ID: mdl-38488493
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, a preneoplastic condition, putting individuals at risk of hepatocellular carcinoma (HCC). 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 with wild-type organoids. Functional enrichment analysis indicated alterations in three main cellular functions (1) interaction with the extracellular matrix, (2) remodeling intermediary metabolism, and (3) cell proliferation and differentiation. The affected cellular processes were validated by orthogonal molecular biology techniques. 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 be targeted for the development of early detection strategies for these severe liver diseases.
Assuntos
Palavras-chave

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Colestase / Colestase Intra-Hepática / Carcinoma Hepatocelular / Subfamília B de Transportador de Cassetes de Ligação de ATP / Neoplasias Hepáticas Limite: Animals / Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Colestase / Colestase Intra-Hepática / Carcinoma Hepatocelular / Subfamília B de Transportador de Cassetes de Ligação de ATP / Neoplasias Hepáticas Limite: Animals / Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article