| Journal: | Annals of hepatology |
| Database: | PERIÓDICA |
| System number: | 000406039 |
| ISSN: | 1665-2681 |
| Authors: | Handa, Priya1 Maliken, Bryan D2 Nelson, James E2 Hennessey, Kelly A1 Vemulakonda, L. Akhila1 Morgan-Stevenson, Vicki1 Dhillon, Barjinder K2 Gupta, Rohit2 Yeh, Matthew M3 Kowdley, Kris V1 |
| Institutions: | 1Swedish Medical Center, Department of Medicine, Seattle, Washington. Estados Unidos de América 2Benaroya Research Institute, Seattle, Washington. Estados Unidos de América 3University of Washington, Medical Center, Seattle, Washington. Estados Unidos de América |
| Year: | 2017 |
| Season: | Ene-Feb |
| Volumen: | 16 |
| Number: | 1 |
| Pages: | 77-85 |
| Country: | México |
| Language: | Inglés |
| Document type: | Artículo |
| Approach: | Aplicado, analítico |
| English abstract | Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. We have previously shown that hepatic reticuloendothelial system (RES) iron deposition is associated with an advanced degree of nonalcoholic steatohepatitis (NASH) in humans. In this study, we aimed to determine differentially expressed genes related to iron overload, inflammation and oxidative stress pathways, with the goal of identifying factors associated with NASH progression. Seventy five patients with NAFLD were evaluated for their biochemical parameters and their liver tissue analyzed for NASH histological characteristics. Gene expression analysis of pathways related to iron homeostasis, inflammation and oxidative stress was performed using real-time PCR. Gene expression was compared between subjects based on disease status and presence of hepatic iron staining. We observed increased gene expression of hepcidin (HAMP) (2.3 fold, p = 0.027), transmembrane serine proteinase 6 (TMPRSS6) (8.4 fold, p = 0.003), signal transducer and activator of transcription 3 (STAT3) (5.5 fold, p = 0.004), proinflammatory cytokines; IL-1β (2.7 fold, p = 0.046) and TNF-α (3.8 fold, p = 0.001) in patients with NASH. TMPRSS6, a negative regulator of HAMP, is overexpressed in patients with NASH and HIF1α (hypoxia inducible factor-1) is downregulated. NAFLD patients with hepatic iron deposition exhibited higher hepcidin expression (3.1 fold, p = 0.04) but lower expression of cytokines. In conclusion, we observed elevated hepatic HAMP expression in patients with NASH and in NAFLD patients who had hepatic iron deposition, while proinflammatory cytokines displayed elevated expression only in patients with NASH, suggesting a regulatory role for hepcidin in NAFL to NASH transition and in mitigating inflammatory responses |
| Disciplines: | Medicina |
| Keyword: | Gastroenterología, Genética, Hígado graso no alcohólico, Esteatohepatitis no alcohólica, Hepcidina, Hierro, Inflamación, Expresión génica |
| Keyword: | Medicine, Gastroenterology, Genetics, Non alcoholic fatty liver, Non-alcoholic steatohepatitis, Hepcidin, Iron, Inflammation, Gene expression |
| Full text: | Texto completo (Ver HTML) |
