Bertran Laia, Pastor Angela, Portillo-Carrasquer Marta, Binetti Jessica, Aguilar Carmen, Martínez Salomé, Vives Margarita, Sabench Fàtima, Porras José Antonio, Riesco David, Del Castillo Daniel, Richart Cristóbal, Auguet Teresa
Grup de Recerca GEMMAIR (AGAUR)-Medicina Aplicada (URV), Departament de Medicina i Cirurgia, Institut d'Investigació Sanitària Pere Virgili (IISPV), Universitat Rovira i Virgili (URV), 43007 Tarragona, Spain.
Servei Medicina Interna, Hospital Universitari Joan XXIII Tarragona, Mallafré Guasch, 4, 43007 Tarragona, Spain.
Int J Mol Sci. 2021 May 15;22(10):5239. doi: 10.3390/ijms22105239.
The pathogenic mechanisms underlying nonalcoholic fatty liver disease (NAFLD) are beginning to be understood. RUNX1 is involved in angiogenesis, which is crucial in inflammation, but its role in nonalcoholic steatohepatitis (NASH) remains unclear. The aim of this study was to analyze RUNX1 mRNA hepatic and jejunal abundance in women with morbid obesity (MO) and NAFLD. RUNX1, lipid metabolism-related genes, and TLRs in women with MO and normal liver (NL, = 28), NAFLD ( = 41) (simple steatosis (SS, = 24), or NASH ( = 17)) were analyzed by RT-qPCR. The RUNX1 hepatic expression was higher in SS than in NL or NASH, as likewise confirmed by immunohistochemistry. An increased expression of hepatic FAS was found in NAFLD. Hepatic RUNX1 correlated positively with FAS. There were no significant differences in the jejunum RUNX1 expressions in the different groups. Jejunal FXR expression was lower in NASH than in NL, while the TLR9 expression increased as NAFLD progressed. Jejunal RUNX1 correlated positively with jejunal PPARγ, TLR4, and TLR5. In summary, the hepatic expression of RUNX1 seems to be involved in the first steps of the NAFLD process; however, in NASH, it seems to be downregulated. Our findings provide important insights into the role of RUNX1 in the context of NAFLD/NASH, suggesting a protective role.
非酒精性脂肪性肝病（NAFLD）的致病机制正逐渐被人们所了解。RUNX1参与血管生成，而血管生成在炎症中至关重要，但其在非酒精性脂肪性肝炎（NASH）中的作用仍不清楚。本研究的目的是分析病态肥胖（MO）和NAFLD女性患者肝脏和空肠中RUNX1 mRNA的丰度。通过RT-qPCR分析了MO且肝脏正常（NL，n = 28）、NAFLD（n = 41）（单纯性脂肪变性（SS，n = 24）或NASH（n = 17））女性患者的RUNX1、脂质代谢相关基因和Toll样受体（TLR）。免疫组织化学同样证实，SS患者肝脏中RUNX1的表达高于NL或NASH患者。在NAFLD患者中发现肝脏脂肪酸合酶（FAS）表达增加。肝脏RUNX1与FAS呈正相关。不同组间空肠RUNX1表达无显著差异。NASH患者空肠法尼醇X受体（FXR）表达低于NL患者，而随着NAFLD进展，TLR9表达增加。空肠RUNX1与空肠过氧化物酶体增殖物激活受体γ（PPARγ）、TLR4和TLR5呈正相关。总之，RUNX1的肝脏表达似乎参与了NAFLD进程的初始步骤；然而，在NASH中，它似乎被下调。我们的研究结果为RUNX1在NAFLD/NASH背景下的作用提供了重要见解，提示其具有保护作用。
