دورية أكاديمية
Macrophage scavenger receptor 1 mediates lipid-induced inflammation in non-alcoholic fatty liver disease
| العنوان: | Macrophage scavenger receptor 1 mediates lipid-induced inflammation in non-alcoholic fatty liver disease |
|---|---|
| المؤلفون: | Govaere, Olivier, Petersen, Sine Kragh, Martinez-Lopez, Nuria, Wouters, Jasper, Van Haele, Matthias, Mancina, Rosellina M., Jamialahmadi, Oveis, Bilkei-Gorzo, Orsolya, Lassen, Pierre Bel, Darlay, Rebecca, Peltier, Julien, Palmer, Jeremy M., Younes, Ramy, Tiniakos, Dina, Aithal, Guruprasad P., Allison, Michael, Vacca, Michele, Goransson, Melker, Berlinguer-Palmini, Rolando, Clark, James E., Drinnan, Michael J., Yki-Jarvinen, Hannele, Dufour, Jean-Francois, Ekstedt, Mattias, Francque, Sven, Petta, Salvatore, Bugianesi, Elisabetta, Schattenberg, Jorn M., Day, Christopher P., Cordell, Heather J., Topal, Baki, Clement, Karine, Romeo, Stefano, Ratziu, Vlad, Roskams, Tania, Daly, Ann K., Anstee, Quentin M., Trost, Matthias, Hartlova, Anetta |
| المصدر: | 0168-8278 ; Journal of hepatology |
| سنة النشر: | 2022 |
| المجموعة: | IRUA - Institutional Repository van de Universiteit Antwerpen |
| مصطلحات موضوعية: | Human medicine |
| الوصف: | Background & Aims: Obesity-associated inflammation is a key player in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). However, the role of macrophage scavenger receptor 1 (MSR1, CD204) remains incompletely understood. Methods: A total of 170 NAFLD liver biopsies were processed for transcriptomic analysis and correlated with clinicopathological features. Msr1(-/-) and wild-type mice were subjected to a 16-week high-fat and high-cholesterol diet. Mice and ex vivo human liver slices were treated with a monoclonal antibody against MSR1. Genetic susceptibility was assessed using genome-wide association study data from 1,483 patients with NAFLD and 430,101 participants of the UK Biobank. Results: MSR1 expression was associated with the occurrence of hepatic lipid-laden foamy macrophages and correlated with the degree of steatosis and steatohepatitis in patients with NAFLD. Mice lacking Msr1 were protected against diet-induced metabolic disorder, showing fewer hepatic foamy macrophages, less hepatic inflammation, improved dyslipidaemia and glucose tolerance, and altered hepatic lipid metabolism. Upon induction by saturated fatty acids, MSR1 induced a pro-inflammatory response via the JNK signalling pathway. In vitro blockade of the receptor prevented the accumulation of lipids in primary macrophages which inhibited the switch towards a proinflammatory phenotype and the release of cytokines such as TNF-alpha Targeting MSR1 using monoclonal antibody therapy in an obesity-associated NAFLD mouse model and human liver slices resulted in the prevention of foamy macrophage formation and inflammation. Moreover, we identified that rs41505344, a polymorphism in the upstream transcriptional region of MSR1, was associated with altered serum triglycerides and aspartate aminotransferase levels in a cohort of over 400,000 patients. Conclusions: Taken together, our data suggest that MSR1 plays a critical role in lipid-induced inflammation and could thus be a potential therapeutic target for the treatment ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/isi/000823493800003 |
| الإتاحة: | https://doi.org/10.1016/J.JHEP.2021.12.012Test https://hdl.handle.net/10067/1897850151162165141Test https://repository.uantwerpen.be/docstore/d:irua:13665Test |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.63F75EF4 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |