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通过 CRISPR/Cas9 沉默 ADAM9 基因可保护小鼠免受酒精性急性肝损伤。

Silencing the ADAM9 Gene through CRISPR/Cas9 Protects Mice from Alcohol-Induced Acute Liver Injury.

机构信息

The Molecular Medicine Key Laboratory of Liver Injury and Repair, School of Basic Medical Sciences, Henan University of Science and Technology, Luoyang 471003, China.

Orthopedic Institute of Henan Province, Luoyang, 471003 Henan, China.

出版信息

Biomed Res Int. 2022 Jun 6;2022:5110161. doi: 10.1155/2022/5110161. eCollection 2022.

DOI:10.1155/2022/5110161
PMID:35707386
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9192226/
Abstract

Alcoholic liver injury is a major global public health concern at present. The ADAM9 gene plays a crucial role in the occurrence and development of various liver diseases, but its role in acute alcoholic liver injury remains ambiguous. In this study, a chimeric single-guide RNA targeting the genomic regions of mouse ADAM9 was designed using the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) technology. Next, the role of ADAM9 in acute alcoholic liver injury in cultured mouse cells and in a hydrodynamic injection-based alcoholic liver injury mouse model was documented. The findings of this study suggest that ADAM9 induces by regulating cell proliferation, apoptosis, and stress metabolism in mice. Thus, inhibiting the expression of ADAM9 gene using CRISPR/Cas9 can attenuate alcohol-induced acute liver injury in mice.

摘要

酒精性肝损伤是目前全球主要的公共卫生关注点。ADAM9 基因在各种肝病的发生和发展中起着关键作用,但它在急性酒精性肝损伤中的作用尚不清楚。在这项研究中,使用成簇规律间隔短回文重复序列(CRISPR)/CRISPR 相关蛋白 9(Cas9)技术设计了针对小鼠 ADAM9 基因组区域的嵌合单引导 RNA。接下来,记录了 ADAM9 在培养的小鼠细胞中的急性酒精性肝损伤和基于水力动力学注射的酒精性肝损伤小鼠模型中的作用。这项研究的结果表明,ADAM9 通过调节小鼠的细胞增殖、凋亡和应激代谢来诱导急性酒精性肝损伤。因此,使用 CRISPR/Cas9 抑制 ADAM9 基因的表达可以减轻小鼠的酒精性急性肝损伤。

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