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Título: | PGE2 induces apoptosis of hepatic stellate cells and attenuates liver fibrosis in mice by downregulating miR-23a-5p and miR-28a-5p |
Autor: | Brea, Rocío CSIC; Motiño, Omar CSIC ORCID CVN; Francés, Daniel E.; García-Monzón, Carmelo; Vargas, Javier; Fernández-Velasco, María CSIC ORCID; Boscá, Lisardo CSIC ORCID CVN ; Casado, Marta CSIC ORCID ; Martín-Sanz, Paloma CSIC ORCID ; Agra, Noelia CSIC | Palabras clave: | COX-2 Liver HSC miRNAs Fibrosis |
Fecha de publicación: | 2018 | Editor: | Elsevier | Citación: | BBA - Molecular Basis of Disease 1864(2): 325-337 (2018) | Resumen: | MicroRNAs (miRNAs), small noncoding RNAs modulating messenger RNA (mRNA) and protein expression, have emerged as key regulatory molecules in chronic liver diseases, whose end stage is hepatic fibrosis, a major global health burden. Pharmacological strategies for prevention or treatment of hepatic fibrosis are still limited, what makes it necessary to establish a better understanding of the molecular mechanisms underlying its pathogenesis. In this context, we have recently shown that cyclooxygenase-2 (COX-2) expression in hepatocytes restricts activation of hepatic stellate cells (HSCs), a pivotal event in the initiation and progression of hepatic fibrosis. Here, we evaluated the role of COX-2 in the regulation of a specific set of miRNAs on a mouse model of CCl4 and bile duct ligation (BDL)-induced liver fibrosis. Our results provide evidence that COX-2 represses miR-23a-5p and miR-28-5p expression in HSC. The decrease of miR-23a-5p and miR-28-5p expression promotes protection against fibrosis by decreasing the levels of pro-fibrogenic markers α-SMA and COL1A1 and increasing apoptosis of HSC. Moreover, we demonstrate that serum levels of miR-28-5p are decreased in patients with chronic liver disease. These results suggest a protective effect exerted by COX-2-derived prostanoids in the process of hepatofibrogenesis. | Descripción: | Título del pdf-manuscrito: PGE2 attenuates liver fibrosis in mice by downregulating miR-23a- 5p and inducing apoptosis of hepatic stellate cells. | Versión del editor: | https://doi.org/10.1016/j.bbadis.2017.11.001 | URI: | http://hdl.handle.net/10261/188345 | DOI: | 10.1016/j.bbadis.2017.11.001 | ISSN: | 0925-4439 |
Aparece en las colecciones: | (IBV) Artículos (IIBM) Artículos |
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pge2miR.pdf | 1,13 MB | Adobe PDF | Visualizar/Abrir |
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