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2024-01-01

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cc by (c) García Sáez, Juan et al, 2024
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/214214

Uncovering a Novel Functional Interaction Between Adult Hepatic Progenitor Cells, Inflammation and EGFR Signaling During Bile Acids-Induced Injury

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https://doi.org/10.7150/ijbs.90645

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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 NLRP3 inflammasome 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-beta 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 contribution for EGFR signaling jointly with bile acids in HPC-mediated actions.

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Malalties del fetge, Macròfags

Matèries (anglès)

Liver diseases, Macrophages

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Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

Citació

GARCÍA SÁEZ, Juan, FIGUEROA FUENTES, María, GONZÁLEZ CORRALEJO, Carlos, RONCERO, Cesáreo, LAZCANOITURBURU, Nerea, GUTIÉRREZ UZQUIZA, Álvaro, VAQUERO, Javier, GONZÁLEZ SÁNCHEZ, Ester, BHUTIA, Kunzangla, CALERO PÉREZ, Silvia, MAINA, Flavio, TRABA, Javier, VALVERDE, Ángela m., FABREGAT, Isabel, HERRERA, Blanca, SÁNCHEZ, Aránzazu. Uncovering a Novel Functional Interaction Between Adult Hepatic Progenitor Cells, Inflammation and EGFR Signaling During Bile Acids-Induced Injury. _International Journal of Biological Sciences_. 2024. Vol. 20, núm. 7, pàgs. 2339-2355. [consulta: 24 de gener de 2026]. ISSN: 1449-2288. [Disponible a: https://hdl.handle.net/2445/214214]

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