Dynamics of compartment-specific proteomic landscapes of hepatotoxic and cholestatic models of liver fibrosis

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F25%3A00619145" target="_blank" >RIV/68378050:_____/25:00619145 - isvavai.cz</a>

Alternative codes found

RIV/00216224:90242/25:00143930 RIV/00216208:11120/25:43928350 RIV/00216208:11310/25:10497281 RIV/00064173:_____/25:43928350 RIV/00023001:_____/25:00085520

Result on the web

<a href="https://doi.org/10.7554/eLife.98023" target="_blank" >https://doi.org/10.7554/eLife.98023</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.7554/eLife.98023" target="_blank" >10.7554/eLife.98023</a>

Result language

angličtina

Original language name

Dynamics of compartment-specific proteomic landscapes of hepatotoxic and cholestatic models of liver fibrosis

Original language description

Accumulation of extracellular matrix (ECM) in liver fibrosis is associated with changes in protein abundance and composition depending upon etiology of the underlying liver disease. Current efforts to unravel etiology-specific mechanisms and pharmacological targets rely on several models of experimental fibrosis. Here, we characterize and compare dynamics of hepatic proteome remodeling during fibrosis development and spontaneous healing in experimental mouse models of hepatotoxic (carbon tetrachloride [CCl4] intoxication) and cholestatic (3,5-diethoxycarbonyl-1,4-dihydrocollidine [DDC] feeding) injury. Using detergent-based tissue extraction and mass spectrometry, we identified compartment-specific changes in the liver proteome with detailed attention to ECM composition and changes in protein solubility. Our analysis revealed distinct time-resolved CCl4 and DDC signatures, with identified signaling pathways suggesting limited healing and a potential for carcinogenesis associated with cholestasis. Correlation of protein abundance profiles with fibrous deposits revealed extracellular chaperone clusterin with implicated role in fibrosis resolution. Dynamics of clusterin expression was validated in the context of human liver fibrosis. Atomic force microscopy of fibrotic livers complemented proteomics with profiles of disease-associated changes in local liver tissue mechanics. This study determined compartment-specific proteomic landscapes of liver fibrosis and delineated etiology-specific ECM components, providing thus a foundation for future antifibrotic therapies.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10608 - Biochemistry and molecular biology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2025

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

eLife

ISSN

2050-084X

e-ISSN

2050-084X

Volume of the periodical

13

Issue of the periodical within the volume

Apr 8

Country of publishing house

GB - UNITED KINGDOM

Number of pages

29

Pages from-to

RP98023

UT code for WoS article

001463169300001

EID of the result in the Scopus database

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