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Title

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

AuthorsBárcena, Cristina CSIC ORCID; Aran, Gemma; Perea, Luís; Sanjurjo, Lucía; Téllez, Érica; Oncins, Anna; Masnou, Helena; Serra, Isabel; García-Gallo, Mónica ; Kremer, Leonor CSIC ORCID ; Salas, Margarita CSIC ORCID ; Armengol, Carolina; Sancho-Bru, Pau; Sarrias, María Rosa
KeywordsMacrophage
Apoptosis inhibitor of macrophages
TGFB
Hepatic stellate cells
SMAD7
Issue DateMay-2019
PublisherElsevier
CitationEBioMedicine 43: 513-524 (2019)
Abstract[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 CCl4-induced fibrosis, and damage, fibrosis and hepatic immune cell infiltration, including the LyC6hi (pro-fibrotic)-LyC6low (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, CCl4-induced damage increased CD5L levels in total liver, particularly in hepatocytes and macrophages. rCD5L administration attenuated CCl4-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 LyC6hi to LyC6low. Interestingly, rCD5L also had a direct effect on primary human hepatic stellate cells promoting SMAD7 expression, thus repressing TGFβ signalling.
Description© 2019 The Authors.
Publisher version (URL)http://dx.doi.org/10.1016/j.ebiom.2019.04.052
URIhttp://hdl.handle.net/10261/240088
Identifiersdoi: 10.1016/j.ebiom.2019.04.052
e-issn: 2352-3964
Appears in Collections:(CNB) Artículos
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