CD5L is a pleiotropic player in liver fibrosis controlling damage, fibrosis and immune cell content

May 17, 2019

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Publicated to: Ebiomedicine. 43 513-524 - 2019-05-01 43(), DOI: 10.1016/j.ebiom.2019.04.052

Authors: Barcena, Cristina; Aran, Gemma; Perea, Luis; Sanjurjo, Lucia; Tellez, Erica; Oncins, Anna; Masnou, Helena; Serra, Isabel; Garcia-Gallo, Monica; Kremer, Leonor; Sala, Margarita; Armengol, Carolina; Sancho-Bru, Pau; Sarrias, Maria-Rosa

Affiliations

CSIC - Centro Nacional de Biotecnologia (CNB) - Author

Ctr Nacl Biotecnol CNB CSIC, Dept Immunol & Oncol, Madrid, Spain - Author

Ctr Nacl Biotecnol CNB CSIC, Prot Tools Unit, Madrid, Spain - Author

Health Science Research Institute Germans Trias i Pujol - Author

Hlth Sci Res Inst Germans Trias & Pujol IGTP, Innate Immun Grp, Badalona, Spain - Author

Hospital Universitari Germans Trias i Pujol - Author

IDIBAPS, Barcelona, Spain - Author

IGTP - Author

IGTP, Program Predict & Personalized Med Canc PMPCC, Childhood Liver Oncol Grp, Barcelona, Spain - Author

Institut d'Investigacions Biomèdiques August Pi i Sunyer - IDIBAPS - Author

Network Biomed Res Diabet & Associated Metab Diso, Barcelona, Spain - Author

Network Biomed Res Hepat & Digest Dis CIBERehd, Barcelona, Spain - Author

Network for Biomedical Research in Diabetes and Associated Metabolic Disorders (CIBERDEM) - Author

Network for Biomedical Research in Hepatic and Digestive Diseases (CIBERehd) - Author

Univ Hosp Germans Trias & Pujol HUGTiP, Dept Gastroenterol, Badalona, Spain - Author

Abstract

© 2019 Background: Chronic hepatic inflammation leads to liver fibrosis, which may progress to cirrhosis, a condition with high morbidity. Our aim was to assess the as yet unknown role of innate immunity protein CD5L in liver fibrosis. Methods: CD5L was measured by ELISA in plasma samples from cirrhotic (n = 63)and hepatitis (n = 39)patients, and healthy controls (n = 7), by immunohistochemistry in cirrhotic tissue (n = 12), and by quantitative RT-PCR in mouse liver cell subsets isolated by cell sorting. Recombinant CD5L (rCD5L)was administered into a murine model of CCl 4 -induced fibrosis, and damage, fibrosis and hepatic immune cell infiltration, including the LyC6 hi (pro-fibrotic)-LyC6 low (pro-resolutive)monocyte ratio were determined. Moreover, rCD5L was added into primary human hepatic stellate cells to study transforming growth factor β (TGFβ)activation responses. Findings: Cirrhotic patients showed elevated plasma CD5L concentrations as compared to patients with hepatitis and healthy controls (Mann-Whitney test p < 0·0001). Moreover, plasma CD5L correlated with disease progression, FIB4 fibrosis score (r:0·25, p < 0·0001)and tissue expression (r = 0·649; p = 0·022). Accordingly, CCl 4 -induced damage increased CD5L levels in total liver, particularly in hepatocytes and macrophages. rCD5L administration attenuated CCl 4 -induced injury and fibrosis as determined by reduced serum transaminase and collagen content. Moreover, rCD5L inhibited immune cell infiltration and promoted a phenotypic shift in monocytes from LyC6 hi to LyC6 low . Interestingly, rCD5L also had a direct effect on primary human hepatic stellate cells promoting SMAD7 expression, thus repressing TGFβ signalling. Interpretation: Our study identifies CD5L as a key pleiotropic inhibitor of chronic liver injury. Fund: Fundació Marató TV3, AGAUR and the ISCIII-EDRF.

Keywords

activationaimapoptosis inhibitor of macrophagesdifferentiationgrowth-factor-betahepatic stellate cellsinflammationmacrophagemacrophagesproteinreceptorssmad7tgf-betatgfbAdultAgedAnimalsApoptosis inhibitor of macrophagesApoptosis inhibitory factorApoptosis regulatory proteinsBiomarkersCd5l protein, humanChemical and drug induced liver injuryCytokinesDisease models, animalDisease susceptibilityFemaleGene expressionHepatic stellate cellsHumansImmunityInflammation mediatorsLiver cirrhosisMacrophageMacrophagesMaleMiceMiddle agedMonocytesReceptors, scavengerScavenger receptors, class bSmad7TgfbYoung adult

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Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Ebiomedicine due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2019, it was in position 18/139, thus managing to position itself as a Q1 (Primer Cuartil), in the category Medicine, Research & Experimental.

From a relative perspective, and based on the normalized impact indicator calculated from World Citations provided by WoS (ESI, Clarivate), it yields a value for the citation normalization relative to the expected citation rate of: 1.38. This indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: ESI Nov 13, 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-12-15, the following number of citations:

WoS: 31
Scopus: 30
Europe PMC: 20

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