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Título: | CD5L is a pleiotropic player in liver fibrosis controlling damage, fibrosis and immune cell content |
Autor: | Bárcena, Cristina CSIC ORCID; Aran, Gemma; Perea, Luís; Sanjurjo, Lucía; Téllez, Érica; Oncins, Anna; Masnou, Helena; Serra, Isabel; García-Gallo, Mónica CSIC ; Kremer, Leonor CSIC ORCID ; Salas, Margarita CSIC ORCID ; Armengol, Carolina; Sancho-Bru, Pau; Sarrias, María Rosa | Palabras clave: | Macrophage Apoptosis inhibitor of macrophages TGFB Hepatic stellate cells SMAD7 |
Fecha de publicación: | may-2019 | Editor: | Elsevier | Citación: | EBioMedicine 43: 513-524 (2019) | Resumen: | [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. | Descripción: | © 2019 The Authors. | Versión del editor: | http://dx.doi.org/10.1016/j.ebiom.2019.04.052 | URI: | http://hdl.handle.net/10261/240088 | DOI: | 10.1016/j.ebiom.2019.04.052 | Identificadores: | doi: 10.1016/j.ebiom.2019.04.052 e-issn: 2352-3964 |
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