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MicroRNA let-7a mediates posttranscriptional inhibition of Nr4A1 and exacerbates cardiac allograft rejection

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收录情况： ◇ SCIE

作者：
Ding Xiangchao[1] * ; Du Yifan[2] * ; Sun Bing[3] * ; Liu Liang[4] ; Le Sheng[5] ; Wu Chuangyan[6] ; Chen Jiuling[6] ; Chen Xing[7] ; Chen Shanshan[8,*2] ; Xia Jiahong[2,*1] ;
机构： [1]Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, China [2]Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China [3]Wuhan Third Hospital (Tongren Hospital of Wuhan University), Wuhan, China [4]Department of Cardiovascular Surgery, Renmin Hospital of Wuhan University, Wuhan, China [5]Department of Thoracic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China [6]Departments of Thoracic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China [7]Department of Cardiovascular Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China [8]Key Laboratory for Molecular Diagnosis of Hubei Province and Central Laboratory, Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
出处：
DOI： 10.1016/j.cellsig.2023.110783
ISSN：

关键词： Heart transplantation Nr4A1 Let-7a CD4+ T cells Posttranscriptional regulation

摘要：
Acute allograft rejection remains a major obstacle after heart transplantation, and CD4+ T cells play a crucial role in allograft rejection. Upregulation of Nr4A1 could regulate CD4+ T-cell function and alleviate allograft rejection. However, the regulatory mechanism of Nr4A1 in allograft rejection remains elusive.BCLb/c mouse hearts were transplanted into WT C57BL/6 mice, and dynamic detection of the changes in Nr4A1 expression revealed that Nr4A1 was regulated posttranscriptionally after heart transplantation. Potential upstream miRNAs of Nr4A1 were screened, and the transfection of cells with these miRNA mimics/inhibitors and dual-luciferase reporter experiments were performed to clarify the regulatory mechanism of miRNAs on Nr4A1 expression. The miRNA agomiR/antagomiR was applied in vivo to validate the role of the corresponding miRNA in heart transplantation. Finally, Nr4A1 knockout mice and an adoptive T-cell cotransfer model were used to confirm the specific effects of miRNA.The expression of Nr4A1 protein (rather than mRNA) exhibited a trend of initially increasing and then decreasing rapidly, and this phenomenon could not be reversed by lysosomal or proteasomal inhibitors. The miRNA let-7a directly binds to the Nr4A1 3'UTR and posttranscriptionally regulates Nr4A1 expression. The let-7a antagomiR prolonged allograft survival and regulated CD4+ T-cell function by upregulating Nr4A1 protein expression in CD4+ T cells.This study confirmed that let-7a is a potential target for interfering with Nr4A1 expression in CD4+ T cells and preventing the pathological progression of cardiac allograft rejection.Copyright © 2023. Published by Elsevier Inc.

基金：
The work was supported by the Hubei Province Natural Science Foundation (2022CFB716 and 2020CFB392), National Natural Science Foundation of China (81730015, 81800296, 82100115 and 82100299), Fundamental Research Funds for the Central Universities (2042020kf0094).
语种：
外文
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中科院(CAS)分区：
出版当年[2022]版：
大类 | 2 区 生物学
小类 | 3 区 细胞生物学
最新[2025]版：
大类 | 2 区 生物学
小类 | 3 区 细胞生物学
JCR分区：
出版当年[2021]版：
Q2 CELL BIOLOGY
最新[2023]版：
Q2 CELL BIOLOGY

影响因子： 最新[2023版] 最新五年平均 出版当年[2021版] 出版当年五年平均 出版前一年[2020版] 出版后一年[2022版]

第一作者：
第一作者机构： [1]Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, China
共同第一作者：
通讯作者：
通讯机构： [2]Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China [8]Key Laboratory for Molecular Diagnosis of Hubei Province and Central Laboratory, Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China [*1]Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277, Jiefang Road, Wuhan 430022, China. [*2]Key Laboratory for Molecular Diagnosis of Hubei Province and Central Laboratory, Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, No. 26 Shengli Street, Wuhan 430014, China.
推荐引用方式(GB/T 7714)：
Ding Xiangchao,Du Yifan,Sun Bing,et al.MicroRNA let-7a mediates posttranscriptional inhibition of Nr4A1 and exacerbates cardiac allograft rejection[J].CELLULAR SIGNALLING.2023,109:doi:10.1016/j.cellsig.2023.110783.
APA：
Ding Xiangchao,Du Yifan,Sun Bing,Liu Liang,Le Sheng...&Xia Jiahong.(2023).MicroRNA let-7a mediates posttranscriptional inhibition of Nr4A1 and exacerbates cardiac allograft rejection.CELLULAR SIGNALLING,109,
MLA：
Ding Xiangchao,et al."MicroRNA let-7a mediates posttranscriptional inhibition of Nr4A1 and exacerbates cardiac allograft rejection".CELLULAR SIGNALLING 109.(2023)

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