Steatosis, inflammasome upregulation, and fibrosis are attenuated in miR-155 deficient mice in a high fat-cholesterol-sugar diet-induced model of NASH.
Steatosis, inflammasome upregulation, and fibrosis are attenuated in miR-155 deficient mice in a high fat-cholesterol-sugar diet-induced model of NASH.
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DOI：
10.1038/s41374-021-00626-1
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发表时间：
2021-12
影响因子：
5
通讯作者：
Szabo, Gyongyi
中科院分区：
文献类型：
--
作者：
Bala, Shashi;Ganz, Michal;Babuta, Mrigya;Zhuang, Yuan;Csak, Timea;Calenda, Charles D.;Szabo, Gyongyi
非酒精性脂肪性肝病（NAFLD）是全球最常见的慢性肝病病因。miRNAs （miRs）调节导致NAFLD的各种细胞事件。在这项研究中，我们验证了miR-155是脂肪性肝炎和纤维化途径的重要调节因子的假设。野生型（WT）或miR-155缺陷型（KO）小鼠接受高脂肪-高胆固醇-高糖饮食（HF-HC-HS） 34周，并分析肝脏组织。在非酒精性脂肪性肝炎患者和HF-HC-HS饮食小鼠模型中，我们发现与正常肝脏相比，肝脏中miR-155水平升高。饲喂HF-HC-HS日粮后，与WT小鼠相比，miR-155 KO小鼠表现出更少的肝损伤，脂肪变性减少，纤维化减弱。在WT小鼠中，ALT、甘油三酯水平和参与脂肪酸代谢途径的基因水平升高，而miR-155 KO小鼠在这些参数中表现出衰减。与鼠粮相比，HF-HC-HS饮食诱导WT小鼠肝脏NLRP3炎性体成分的表达显著增加。与WT小鼠相比，miR-155 KO在HF-HC-HS饮食中对NLRP3、ASC和caspase1炎症小体表达的诱导减弱。WT小鼠的胶原含量和沉积、αSMA、Zeb2、vimentin等纤维化标志物均升高，miR-155 KO小鼠的纤维化标志物表达减弱。总的来说，我们的研究结果强调了miR-155在HF-HC-HS饮食诱导的脂肪变性和肝纤维化中的作用。非酒精性脂肪性肝病是全球慢性肝病最常见的病因，也是肝细胞癌的危险因素。该研究强调了miR-155在非酒精性脂肪性肝炎中的作用。mir -155缺陷小鼠显示出对饮食诱导的脂肪性肝炎和纤维化的全面保护。治疗性抑制miR-155可能是治疗非酒精性脂肪性肝炎的有效途径。
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease globally. miRNAs (miRs) regulate various cellular events that lead to NAFLD. In this study we tested the hypothesis that miR-155 is an important regulator of steatohepatitis and fibrosis pathways. Wild type (WT) or miR-155 deficient (KO) mice received a high fat-high cholesterol-high sugar-diet (HF-HC-HS) for 34 weeks and liver tissues were analyzed. In patients with non-alcoholic steatohepatitis and in the mouse model of HF-HC-HS diet we found increased miR-155 levels in the liver compared to normal livers. Upon HF-HC-HS diet feeding, miR-155 KO mice displayed less liver injury, decreased steatosis, and attenuation in fibrosis compared to WT mice. ALT, triglyceride levels and genes involved in fatty acid metabolic pathway were increased in WT mice whereas miR-155 KO mice showed attenuation in these parameters. HF-HC-HS diet induced significant increase in the expression of NLRP3 inflammasome components in the livers of WT mice compared to chow fed diet. Compared to WT mice, miR-155 KO showed attenuated induction in the NLRP3, ASC and caspase1 inflammasome expression on HF-HC-HS diet. Fibrosis markers such as collagen content and deposition, αSMA, Zeb2, and vimentin were all increased in WT mice and miR-155 KO mice showed attenuated fibrosis marker expression. Overall, our findings highlight a role for miR-155 in HF-HC-HS diet-induced steatosis and liver fibrosis. Non-alcoholic fatty liver disease is the most common cause of chronic liver disease globally and a risk factor for hepatocellular carcinoma. The study highlights the role of miR-155 in non-alcoholic steatohepatitis. miR-155-deficient mice displayed overall protection from diet-induced steatohepatitis and fibrosis. Therapeutic inhibition of miR-155 might be effective approach for treatment of non-alcoholic steatohepatitis.
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影响因子：
25.7
作者：
Bala S;Csak T;Saha B;Zatsiorsky J;Kodys K;Catalano D;Satishchandran A;Szabo G
通讯作者：
Szabo G
影响因子：
4.9
作者：
Christmann RB;Wooten A;Sampaio-Barros P;Borges CL;Carvalho CR;Kairalla RA;Feghali-Bostwick C;Ziemek J;Mei Y;Goummih S;Tan J;Alvarez D;Kass DJ;Rojas M;de Mattos TL;Parra E;Stifano G;Capelozzi VL;Simms RW;Lafyatis R
通讯作者：
Lafyatis R
影响因子：
7.3
作者：
Alivernini S;Gremese E;McSharry C;Tolusso B;Ferraccioli G;McInnes IB;Kurowska-Stolarska M
通讯作者：
Kurowska-Stolarska M
DOI：
10.1016/j.jaci.2016.09.021
发表时间：
2017-06
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
Kurowska-Stolarska M;Hasoo MK;Welsh DJ;Stewart L;McIntyre D;Morton BE;Johnstone S;Miller AM;Asquith DL;Millar NL;Millar AB;Feghali-Bostwick CA;Hirani N;Crick PJ;Wang Y;Griffiths WJ;McInnes IB;McSharry C
通讯作者：
McSharry C
影响因子：
5.4
作者：
Luo, Quan;Zeng, Jingxin;Zhang, Xibao
通讯作者：
Zhang, Xibao