Manicardi, Nicolò; Fernández-Iglesias, Anabel; Abad-Jordà, Laia; Royo, Felix; Azkargorta, Mikel; Ortega-Ribera, Martí; Sanfeliu-Redondo, David; Martínez-Alcocer, Ana; Elortza, Felix; Hessheimer, Amelia J; Fondevila, Constantino; Lozano, Juan José; García-Pagán, Juan Carlos; Bosch, Jaime; Cubero, Francisco Javier; Albillos, Agustín; Vaquero, Javier; Falcón-Pérez, Juan M; Gracia-Sancho, Jorge (2021). Transcriptomic Profiling of the Liver Sinusoidal Endothelium during Cirrhosis Reveals Stage-Specific Secretory Signature. Cancers, 13(11) MDPI AG 10.3390/cancers13112688
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The poor prognosis of chronic liver disease (CLD) generates the need to investigate the evolving mechanisms of disease progression, thus disclosing therapeutic targets before development of clinical complications. Considering the central role of liver sinusoidal endothelial cells (LSECs) in pre-neoplastic advanced CLD, the present study aimed at investigating the progression of CLD from an endothelial holistic perspective. RNAseq defined the transcriptome of primary LSECs isolated from three pre-clinical models of advanced CLD, during the progression of the disease, and from fresh human cirrhotic tissue. At each stage of the disease, the effects of LSECs secretome on neighboring cells and proteomic analysis of LSECs-derived extracellular vesicles (EVs) were also determined. CLD was associated with deep common modifications in the transcriptome of LSECs in the pre-clinical models. Pathway enrichment analysis showed predominance of genes related with pro-oncogenic, cellular communication processes, and EVs biogenesis during CLD progression. Crosstalk experiments revealed endothelial EVs as potent angiocrine effectors. The proteome of LSECs EVs showed stage-specific signatures, including over-expression of tropomyosin-1. Proof-of-principle experiments treating cirrhotic HSCs with recombinant tropomyosin-1 suggested de-activating effects. Our data provide the basis for discovering novel biomarkers and therapeutic targets for new disease-modifying treatments for patients with advanced CLD.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Hepatology 04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Hepatologie 04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Hepatologie |
UniBE Contributor: |
Bosch Genover, Jaime, Gracia Sancho, Jorge Sergio |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
2072-6694 |
Publisher: |
MDPI AG |
Language: |
English |
Submitter: |
Rahel Fuhrer |
Date Deposited: |
13 Oct 2021 10:56 |
Last Modified: |
02 Mar 2023 23:35 |
Publisher DOI: |
10.3390/cancers13112688 |
PubMed ID: |
34072510 |
Uncontrolled Keywords: |
LSEC RNAseq extracellular vesicles hepatic stellate cell |
BORIS DOI: |
10.48350/159666 |
URI: |
https://boris.unibe.ch/id/eprint/159666 |
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