Deletion of miR-126a Promotes Hepatic Aging and Inflammation in a Mouse Model of Cholestasis

doi:10.1016/j.omtn.2019.04.002

	Deletion of miR-126a Promotes Hepatic Aging and Inflammation in a Mouse Model of Cholestasis
	Yan, Yi 1; Qin, Dan 1; Hu, Bian 2; Zhang, Chunjing 1; Liu, Shenghui 1; Wu, Dongde 3; Huang, Wendong 4; Huang, Xingxu2 ; Wang, Liqiang 5; Chen, Xiangmei 5; Zhang, Lisheng 1
	2019-06-07
发表期刊	MOLECULAR THERAPY-NUCLEIC ACIDS (IF:6.5[JCR-2023],6.7[5-Year])
ISSN	2162-2531
卷号	16 页码:494-504
发表状态	已发表
DOI	10.1016/j.omtn.2019.04.002
摘要	MicroRNAs (miRNAs) act as regulators of aging at the tissue or organism level or as regulators of cellular senescence. Targeted deletion of miR-126 in mice causes partial embryonic lethality, but its biological function in the liver is still largely unknown. Here, we deleted miR-126a, using the CRISPR/Cas9 system in vitro and in vivo. miR-126a was reduced in the aging livers, and disruption of miR-126a in bone mesenchymal stem cells (BMSCs) induced age-associated telomere shortening, DNA damage responses, and proinflammatory cytokines. Moreover, disruption of miR-126a in mice caused hepatocyte senescence, inflammation, and metabolism deficiency. In addition, disruption of miR-126a via BMSC transplantation aggravated the severity of liver defects induced by cholestasis compared with that in the functional miR-126a BMSC group. Mechanistically, we identified versican (VCAN) as a novel direct miR-126a-5p target that induces telomere shortening, BMSC senescence, and nuclear factor kappa B (NF-kappa B) pathway activation. This study identified aging-related reduced expression of miR-126a and promotion of its target VCAN as a key mechanism in the regulation of hepatic metabolic function during aging and hepatic damage by inducing NF-kappa B pathway activation, DNA repair function disorder, and telomere attrition. The findings indicate that miR-126a may be a drug target for the treatment of hepatic failure.
收录类别	SCI ; SCIE
语种	英语
资助项目	Fundamental Research Funds for the Central Universities[2662017PY106] ; Fundamental Research Funds for the Central Universities[2662016PY087] ; Fundamental Research Funds for the Central Universities[2662019YJ008]
WOS研究方向	Research & Experimental Medicine
WOS类目	Medicine, Research & Experimental
WOS记录号	WOS:000470250900044
出版者	CELL PRESS
WOS关键词	MESENCHYMAL STEM-CELLS ; HEPATOCELLULAR-CARCINOMA ; SENESCENCE ; LIVER ; MICRORNAS ; AGE ; ATHEROSCLEROSIS ; PROLIFERATION ; TELOMERES ; VERSICAN
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/48977
专题	生命科学与技术学院_PI研究组_黄行许组
通讯作者	Zhang, Lisheng
作者单位	1.Huazhong Agr Univ, Coll Vet Med, Biomed Ctr, Wuhan 430070, Hubei, Peoples R China 2.Shanghai Tech Univ, Sch Life Sci & Technol, 100 Haike Rd, Shanghai 201210, Peoples R China 3.Wuhan Univ, Hubei Canc Hosp, Canc Hosp, Dept Hepatobiliary & Pancreat Surg, Wuhan 430079, Hubei, Peoples R China 4.City Hope Natl Med Ctr, Diabet & Metab Res Inst, Beckman Res Inst, Dept Diabet Complicat & Metab, Duarte, CA 91010 USA 5.Chinese Peoples Liberat Army Gen Hosp, Chinese PLA Inst Nephrol, Dept Nephrol, State Key Lab Kidney Dis,Natl Clin Res Ctr Kidney, 28th Fuzing Rd, Beijing 100853, Peoples R China
推荐引用方式 GB/T 7714	Yan, Yi,Qin, Dan,Hu, Bian,et al. Deletion of miR-126a Promotes Hepatic Aging and Inflammation in a Mouse Model of Cholestasis[J]. MOLECULAR THERAPY-NUCLEIC ACIDS,2019,16:494-504.
APA	Yan, Yi.,Qin, Dan.,Hu, Bian.,Zhang, Chunjing.,Liu, Shenghui.,...&Zhang, Lisheng.(2019).Deletion of miR-126a Promotes Hepatic Aging and Inflammation in a Mouse Model of Cholestasis.MOLECULAR THERAPY-NUCLEIC ACIDS,16,494-504.
MLA	Yan, Yi,et al."Deletion of miR-126a Promotes Hepatic Aging and Inflammation in a Mouse Model of Cholestasis".MOLECULAR THERAPY-NUCLEIC ACIDS 16(2019):494-504.