Melatonin limits the expression of profibrogenic genes and ameliorates the progression of hepatic fibrosis in mice

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Melatonin limits the expression of profibrogenic genes and ameliorates the progression of hepatic fibrosis in mice

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Title: Melatonin limits the expression of profibrogenic genes and ameliorates the progression of hepatic fibrosis in mice
Author: Crespo, Irene;San-Miguel, Beatriz;Fernández, Ana;Ortiz de Urbina, Juan;González-Gallego, Javier;Tuñón, María J.
xmlui.dri2xhtml.METS-1.0.item-contributor: Instituto Universitario de Biomedicina (IBIOMED)
xmlui.dri2xhtml.METS-1.0.item-area: Otros
Abstract: We investigated whether melatonin ameliorates fibrosis and limits the expression of fibrogenic genes in mice treated with carbon tetrachloride (CCl4). Mice in treatment groups received CCl4 5 mL/g body weight intraperitoneally twice a week for 4 or 6 weeks. Melatonin was given at 5 or 10 mg/kg/d intraperitoneally, beginning 2 weeks after the start of CCl4 administration. Treatment with CCl4 resulted in fibrosis evidenced by the staining of Van Gieson and a-smooth muscle actin (a-SMA) positive cells in the liver. At both 4 and 6 weeks, CCl4 induced an increase in the messenger RNA levels of collagens I and III, transforming growth factor (TGF)-b, platelet-derived growth factor (PDGF), connective tissue growth factor (CTGF), amphiregulin, matrix metalloproteinase (MMP)-9, and tissue inhibitor of metalloproteinase (TIMP)-1. Protein concentrations of CTGF, amphiregulin, MMP-9, TIMP-1, and phospho-Smad3 were also significantly augmented in fibrotic mice. Melatonin successfully attenuated liver injury, as shown by histopathology and decreased levels of serum transaminases. Immunohistochemical staining of a-SMA indicated an abrogation of hepatic stellate cell activation by the indol. Furthermore, melatonin treatment resulted in significant inhibition of the expression of collagens I and III, TGF-b, PDGF, CTGF, amphiregulin, and phospho-Smad3. The MMP-9 activity decreased and the expression of nuclear factor erythroid–2–related factor 2 (Nrf2) increased in mice receiving melatonin. Data obtained suggest that attenuation of multiple profibrogenic gene pathways contributes to the beneficial effects of melatonin in mice with CCl4-induced liver fibrosis
xmlui.dri2xhtml.METS-1.0.item-desfisica: P. 346-357
xmlui.dri2xhtml.METS-1.0.item-peerreviewed: SI
Publisher: Elsevier
xmlui.dri2xhtml.METS-1.0.item-citation: Translational Research, 2015, vol. 165, n. 2
URI: http://hdl.handle.net/10612/5691
Date: 2015-10-23
xmlui.dri2xhtml.METS-1.0.item-tipo: info:eu-repo/semantics/article
Subject: Medicina. Salud
xmlui.dri2xhtml.METS-1.0.item-palclave: Melatonin
Profibrogenic
Hepatic fibrosis
Ameliorates
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