Angiotensin-Converting Enzyme 2 Enhances Autophagy via the Consumption of miR-326 in a Mouse Model of Acute Lung Injury

被引:0
作者
Lin, Xingsheng [1 ]
Gao, Fengying [2 ]
机构
[1] Fuzhou Univ, Affiliated Prov Hosp, Dept Intens Care Unit, Fuzhou 350001, Fujian, Peoples R China
[2] Shanghai Univ Tradit Chinese Med, Shanghai Municipal Hosp Tradit Chinese Med, Dept Pulm Dis, Shanghai 200071, Peoples R China
关键词
Angiotensin-converting enzyme 2; Acute lung injury; Autophagy; MiRNA; Lung vascular endothelial cells; MESENCHYMAL STEM-CELLS; ISCHEMIA-REPERFUSION INJURY; PULMONARY ENDOTHELIAL-CELLS; INHIBITS APOPTOSIS; ACE2; MTOR; GENE;
D O I
10.1007/s10528-025-11040-3
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Angiotensin-converting enzyme 2 (ACE2) has been reported to exert a protective effect in acute lung injury (ALI), though its underlying mechanism remains incompletely understood. In this study, ACE2 expression was found to be upregulated in a mouse model of ALI induced by lipopolysaccharide (LPS) injection. ACE2 knockdown modulated the severity of ALI, the extent of autophagy, and the mTOR pathway in this model. ACE2 regulated liver kinase B1 (LKB1) gene expression by sequestering miR-326, thereby alleviating ALI severity through enhanced autophagy. In cell-based experiments, miR-326 was shown to regulate ACE2 and LKB1 expression and autophagy. Overexpression of ACE2 disrupted miR-326's regulatory effect on LKB1, suggesting that LKB1 may function as an endogenous sponge for miR-326. These findings imply that elevated ACE2 expression in lung could play enhance the autophagy via the consumption of miR-326.
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页数:18
相关论文
共 43 条
[1]   HMEC-1 - ESTABLISHMENT OF AN IMMORTALIZED HUMAN MICROVASCULAR ENDOTHELIAL-CELL LINE [J].
ADES, EW ;
CANDAL, FJ ;
SWERLICK, RA ;
GEORGE, VG ;
SUMMERS, S ;
BOSSE, DC ;
LAWLEY, TJ .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 1992, 99 (06) :683-690
[2]   miRNA sponges: soaking up miRNAs for regulation of gene expression [J].
Bak, Rasmus O. ;
Mikkelsen, Jacob Giehm .
WILEY INTERDISCIPLINARY REVIEWS-RNA, 2014, 5 (03) :317-333
[3]   Angiotensin-Converting Enzyme 2 Inhibits Apoptosis of Pulmonary Endothelial Cells During Acute Lung Injury Through Suppressing MiR-4262 [J].
Bao, Hong ;
Gao, Fengying ;
Xie, Guogang ;
Liu, Zhenwei .
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY, 2015, 37 (02) :759-767
[4]   Expression profiling and microRNA regulation of the LKB1 pathway in young and aged lung adenocarcinoma patients [J].
Boldrini, Laura ;
Giordano, Mirella ;
Lucchi, Marco ;
Melfi, Franca ;
Fontanini, Gabriella .
BIOMEDICAL REPORTS, 2018, 9 (03) :198-205
[5]   A tool for design of primers for microRNA-specific quantitative RT-qPCR [J].
Busk, Peter K. .
BMC BIOINFORMATICS, 2014, 15
[6]   Acute Lung Injury A Clinical and Molecular Review [J].
Butt, Yasmeen ;
Kurdowska, Anna ;
Allen, Timothy Craig .
ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE, 2016, 140 (04) :345-350
[7]   Micro-RNA-195 and-451 Regulate the LKB1/AMPK Signaling Axis by Targeting MO25 [J].
Chen, Hao ;
Untiveros, Gustavo M. ;
McKee, Laurel A. K. ;
Perez, Jessica ;
Li, Jing ;
Antin, Parker B. ;
Konhilas, John P. .
PLOS ONE, 2012, 7 (07)
[8]   ComiR: combinatorial microRNA target prediction tool [J].
Coronnello, Claudia ;
Benos, Panayiotis V. .
NUCLEIC ACIDS RESEARCH, 2013, 41 (W1) :W159-W164
[9]   Angiotensin-converting enzyme 2 attenuates inflammatory response and oxidative stress in hyperoxic lung injury by regulating NF-κB and Nrf2 pathways [J].
Fang, Y. ;
Gao, F. ;
Liu, Z. .
QJM-AN INTERNATIONAL JOURNAL OF MEDICINE, 2019, 112 (12) :914-924
[10]  
Fang Y, 2017, AM J TRANSL RES, V9, P1287