RT Journal Article
T1 Uncovering a Novel Functional Interaction Between Adult Hepatic Progenitor Cells, Inflammation and EGFR Signaling During Bile Acids-Induced Injury
A1 García-Sáez, Juan
A1 Figueroa-Fuentes, María
A1 González-Corralejo, Carlos
A1 Roncero Romero, Cesáreo
A1 Lazcanoiturburu, Nerea
A1 Gutiérrez Uzquiza, Álvaro
A1 Vaquero, Javier
A1 González-Sánchez, Ester
A1 Bhutia, Kunzangla
A1 Calero-Pérez, Silvia
A1 Maina, Flavio
A1 Traba, Javier
A1 Martínez Valverde, Ángela María
A1 Fabregat Romero, María Isabel
A1 Herrera González, Blanca María
A1 Sánchez Muñoz, Aranzazu
AB Chronic cholestatic damage is associated to both accumulation of cytotoxic levels of bile acids and expansion of adult hepatic progenitor cells (HPC) as part of the ductular reaction contributing to the regenerative response. Here, we report a bile acid-specific cytotoxic response in mouse HPC, which is partially impaired by EGF signaling. Additionally, we show that EGF synergizes with bile acids to trigger inflammatory signaling and NLRP3inflammasome activation in HPC. Aiming at understanding the impact of this HPC specific response on the liver microenvironment we run a  proteomic analysis of HPC secretome. Data show an enrichment in immune and TGF-β regulators, ECM components and remodeling proteins in HPC secretome. Consistently, HPC-derived conditioned medium promotes hepatic stellate cell (HSC) activation and macrophage M1-like polarization.Strikingly, EGF and bile acids co-treatment leads to profound changes in the secretome composition, illustrated by an abolishment of HSC activating effect and by promoting macrophage M2-like polarization. Collectively, we provide new specific mechanisms behind HPC regulatory action during cholestatic liver injury, with an active role in cellular interactome and inflammatory response regulation. Moreover, findings prove a key contributionfor EGFR signaling jointly with bile acids in HPC-mediated actions.
PB Ivyspring
SN 1449-2288
YR 2024
FD 2024-04
LK https://hdl.handle.net/20.500.14352/107189
UL https://hdl.handle.net/20.500.14352/107189
LA eng
NO García-Sáez, Juan, et al. «Uncovering a Novel Functional Interaction Between Adult Hepatic Progenitor Cells, Inflammation and EGFR Signaling During Bile Acids-Induced Injury». International Journal of Biological Sciences, vol. 20, n.o 7, 2024, pp. 2339-55. DOI.org (Crossref), https://doi.org/10.7150/ijbs.90645.
NO Ministerio de Ciencia e Innovación
NO European Commission-ERC
NO Fundación Ramón Areces
DS Docta Complutense
RD 10 abr 2025