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在缺氧诱导的肝纤维化中可通过NF-κB信号通路进行调节。

- can be regulated by via the NF-κB pathway in hypoxia-induced liver fibrosis.

作者信息

Ba Hong-Zhen, Liang Zhi-Hui, Kim Hyung Sik, Cao Wei

机构信息

Department of Medical Imaging, Yan'an University Medical College, Yan'an, China.

Department of Radiology, The 980 Hospital of PLA Logistic Force, Shijiazhuang, China.

出版信息

Ann Transl Med. 2021 Mar;9(6):505. doi: 10.21037/atm-21-1298.

Abstract

BACKGROUND

The identification of the important elements that control hepatic stellate cell (HSC) activation will expand our understanding of the mechanism of liver fibrosis induced by hypoxia and affect the outcome of clinical treatment. A previous research demonstrated that N-Myc downstream-regulated gene 2 () is a potential regulator of fibrosis and a downstream target gene of hypoxia-inducible factor 1 (). In this research, we studied the expression and function of NDRG2 in liver fibrosis induced by hypoxia.

METHODS

LX-2 cells/NF-κB-silenced LX-2 cells were exposed to hypoxic conditions (1% O) to activate HSCs . The protein and mRNA expression levels of , and transforming growth factor beta 1 () were evaluated by western blotting and real-time polymerase chain reaction (RT-PCR), respectively. Functional studies were performed using adenovirus-mediated gene upregulation.

RESULTS

The mRNA and protein levels were reduced under hypoxic conditions in LX-2 cells and overexpression of resulted in a decrease in the expression of and . Interestingly, no relationship was observed between and when the NF-κB pathway was blocked, which indicates that can regulate the expression of in LX-2 cells via the NF-κB pathway under hypoxic conditions.

CONCLUSIONS

may regulate the expression of via the NF-κB pathway and may be a novel therapeutic target for liver fibrosis induced by hypoxia.

摘要

背景

确定控制肝星状细胞(HSC)激活的重要因素将拓宽我们对缺氧诱导肝纤维化机制的理解,并影响临床治疗结果。先前的一项研究表明,N-Myc下游调节基因2()是纤维化的潜在调节因子,也是缺氧诱导因子1()的下游靶基因。在本研究中,我们研究了NDRG2在缺氧诱导的肝纤维化中的表达及功能。

方法

将LX-2细胞/ NF-κB沉默的LX-2细胞置于缺氧条件(1% O)下以激活肝星状细胞。分别通过蛋白质印迹法和实时聚合酶链反应(RT-PCR)评估、和转化生长因子β1()的蛋白质和mRNA表达水平。使用腺病毒介导的基因上调进行功能研究。

结果

在缺氧条件下,LX-2细胞中的mRNA和蛋白质水平降低,而的过表达导致和的表达降低。有趣的是,当NF-κB途径被阻断时,未观察到与之间的关系,这表明在缺氧条件下可通过NF-κB途径调节LX-2细胞中的表达。

结论

可能通过NF-κB途径调节的表达,并且可能是缺氧诱导的肝纤维化的新型治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae93/8039646/51f47e0fdcd6/atm-09-06-505-f1.jpg

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