Upregulated microRNA-450b-5p represses the development of acute liver failure via modulation of liver function, inflammatory response, and hepatocyte apoptosis

被引:0
作者
Fang, Jun [1 ]
Kuang, Jing [2 ,4 ]
Hu, Shuli [2 ]
Yang, Xiuhong [2 ]
Wan, Weibo [2 ]
Li, Jing [3 ]
Fan, Xuepeng [2 ]
机构
[1] Wu Han Hosp Tradit Chinese Med, Dept Liver Gallbladder & Gastr Dis, Wuhan, Hubei, Peoples R China
[2] Wuhan No 1 Hosp, Dept Intens Care Unit, Wuhan, Hubei, Peoples R China
[3] Wuhan No 1 Hosp, Dept Internal Med Cardiovasc, Wuhan, Hubei, Peoples R China
[4] Wuhan No 1 Hosp, Dept Intens Care Unit, 215Zhongshan Ave,Qiaokou Dist, Wuhan 430022, Hubei, Peoples R China
关键词
acute liver failure; apoptosis; inflammatory response; microRNA-450b-5p; Mouse Double Minute 2 protein; pathological change; MDM2;
D O I
10.1002/iid3.767
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
ObjectiveIt has been evidenced that microRNAs (miRs) exert crucial effects on acute liver failure (ALF), while the detailed function of miR-450b-5p in ALF progression remained obscure. The purpose of this research was to unravel the regulatory mechanism of miR-450b-5p in ALF via modulating Mouse Double Minute 2 protein (MDM2). MethodsALF was induced in mice by intraperitoneal injection of d-galactosamine (d-GalN) and lipopolysaccharide (LPS). Adenoviruses containing overexpressed miR-450b-5p, MDM2 shRNA, and overexpressed MDM2 sequences were utilized to manipulate miR-450b-5p and MDM2 expression in the liver before the mice were treated withd-GalN/LPS-induced ALF. Subsequently, miR-450b-5p and MDM2 expression levels in liver tissues of ALF mice were examined. Serum biochemical parameters of liver function were tested, serum inflammatory factors were assessed, and the histopathological changes and hepatocyte apoptosis in liver tissues were observed. The relation between miR-450b-5p and MDM2 was verified. ResultsIn ALF mice, miR-450b-5p was low-expressed while MDM2 was high-expressed. The upregulation of miR-450b-5p or downregulation of MDM2 could alleviate liver function, mitigate the serum inflammatory response and pathological changes in liver tissues, as well as inhibit the apoptosis of hepatocytes. MiR-450b-5p targeted MDM2. MDM2 overexpression reversed the repressive effects of elevated miR-450b-5p on ALF. ConclusionThe upregulated miR-450b-5p blocks the progression of ALF via targeting MDM2. This study contributes to affording novel therapeutic targets for ALF treatment.
引用
收藏
页数:10
相关论文
共 35 条
  • [1] Acute Liver Failure
    Bernal, William
    Wendon, Julia
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 2013, 369 (26) : 2525 - 2534
  • [2] The role of MDM2-p53 axis dysfunction in the hepatocellular carcinoma transformation
    Cao, Hui
    Chen, Xiaosong
    Wang, Zhijun
    Wang, Lei
    Xia, Qiang
    Zhang, Wei
    [J]. CELL DEATH DISCOVERY, 2020, 6 (01)
  • [3] Hepatic miRNA expression reprogrammed by Plasmodium chabaudi malaria
    Delic, Denis
    Dkhil, Mohamed
    Al-Quraishy, Saleh
    Wunderlich, Frank
    [J]. PARASITOLOGY RESEARCH, 2011, 108 (05) : 1111 - 1121
  • [4] Iron-Dependent Regulation of MDM2 Influences p53 Activity and Hepatic Carcinogenesis
    Dongiovanni, Paola
    Fracanzani, Anna Ludovica
    Cairo, Gaetano
    Megazzini, Chiara Paola
    Gatti, Stefano
    Rametta, Raffaela
    Fargion, Silvia
    Valenti, Luca
    [J]. AMERICAN JOURNAL OF PATHOLOGY, 2010, 176 (02) : 1006 - 1017
  • [5] Ebrahim M, 2015, HISTOL HISTOPATHOL, V30, P1271, DOI 10.14670/HH-11-636
  • [6] Acute Liver Failure
    Grek, Ami
    Arasi, Lisa
    [J]. AACN ADVANCED CRITICAL CARE, 2016, 27 (04) : 420 - 429
  • [7] Inhibition of miR-450b-5p ameliorates hepatic ischemia/reperfusion injury via targeting CRYAB
    Huang, Zuotian
    Mou, Tong
    Luo, Yunhai
    Pu, Xingyu
    Pu, Junliang
    Wan, Lei
    Gong, Junhua
    Yang, Hang
    Liu, Yanyao
    Li, Zhongtang
    Shen, Ai
    Wu, Zhongjun
    [J]. CELL DEATH & DISEASE, 2020, 11 (06)
  • [8] Serum ROCK2, miR-300 and miR-450b-5p levels in two different clinical phenotypes of multiple sclerosis: Relation to patient disability and disease progression
    Ibrahim, Samar H.
    El-Mehdawy, Karim M.
    Seleem, Mae
    El-Sawalhi, Maha M.
    Shaheen, Amira A.
    [J]. JOURNAL OF NEUROIMMUNOLOGY, 2020, 347
  • [9] miR-450b-5p loss mediated KIF26B activation promoted hepatocellular carcinoma progression by activating PI3K/AKT pathway
    Li, Hua
    Shen, Shen
    Chen, Xiaolong
    Ren, Zhigang
    Li, Zhiqin
    Yu, Zujiang
    [J]. CANCER CELL INTERNATIONAL, 2019, 19 (1)
  • [10] Therapeutic effect of Sirtuin 3 on ameliorating nonalcoholic fatty liver disease: The role of the ERK-CREB pathway and Bnip3-mediated mitophagy
    Li, Ruibing
    Xin, Ting
    Li, Dandan
    Wang, Chengbin
    Zhu, Hang
    Zhou, Hao
    [J]. REDOX BIOLOGY, 2018, 18 : 229 - 243