机构：[1]Pathology Department, First Hospital of Shanxi Medical University, Taiyuan, Shanxi Province, 030001, China.[2]Medical oncology, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, 050011, China.河北医科大学第四医院肿瘤内科临床科室[3]Urology Department, First Hospital of Shanxi Medical University, Taiyuan, Shanxi Province, 030001, China.[4]Department of urinary surgery, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, 050011, China.临床科室泌尿外科河北医科大学第四医院
What is the central question of this study? How does miR-302a-3p play a role in hypoxia/reoxygenation-induced pyroptosis of renal tubular epithelial cells? What is the main finding and its importance? We found that H/R treatment could upregulate the expression of miR-302a-3p in HK-2 cells, and then inhibited the transcription of FMR1, so as to promote the activation of NLRP3 inflammasome and aggravate the pyroptosis of HK-2 cells. miR-302a-3p was used as a molecular target in this study, which provides a new theoretical basis for the treatment of renal failure.Hypoxia/reoxygenation (H/R) induction can affect miRNA expression and then control NLRP3 inflammasome-mediated pyroptosis. This study investigated the mechanism of miR-302a-3p in H/R-induced renal tubular epithelial cell (RTEC) pyroptosis. Human RTECs HK-2 were induced by H/R. LDH content, cell activity and pyroptosis, and levels of NLRP3, GSDMD-N, caspase-1, IL-1β, IL-18, SOD and MDA were detected to verify the effect of H/R on HK-2 cells. The NLRP3 inflammasome action was evaluated after H/R-induced HK-2 cells were treated by BAY11-7082, an inflammasome inhibitor. After inhibiting miR-302a-3p expression, the changes of pyroptosis were observed. The binding relation between miR-302a-3p and FMR1 was verified. The function rescue experiment verified the role of FMR1 in the regulation of pyroptosis. H/R-induced HK-2 cells showed significant pyroptosis injury, and NLRP3 inflammasome was activated. After inhibiting NLRP3 inflammasome, H/R-induced apoptosis was inhibited. After H/R treatment, miR-302a-3p in HK-2 cells was increased, and miR-302a-3p downregulation limited H/R-induced NLRP3 inflammasome-mediated pyroptosis. FMR1 is the target of miR-302a-3p. Inhibition of FMR1 alleviated the inhibition of H/R-induced HK-2 cell pyroptosis by miR-302a-3p inhibitor. Collectively, inhibiting miR-302a-3p can weaken its targeted inhibition on FMR1, thereby inhibiting the activation of NLRP3 inflammasome and reducing caspase-1-dependent pyroptosis in HK-2 cells. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.
基金：
Scientific Research Program of Shanxi
Provincial Health Commission, Grant/Award
Number: 2017035; Shanxi Provincial Basic
Applied Research Project, Grant/Award
Number: 201801D121331
第一作者机构：[1]Pathology Department, First Hospital of Shanxi Medical University, Taiyuan, Shanxi Province, 030001, China.
共同第一作者：
通讯作者：
通讯机构：[3]Urology Department, First Hospital of Shanxi Medical University, Taiyuan, Shanxi Province, 030001, China.[4]Department of urinary surgery, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, 050011, China.[*1]Urology Department, First Hospital of ShanxiMedical University, No. 85, Jiefangnan Road, Yingze District, Taiyuan 030001, Shanxi, China[*2]Department of Urinary Surgery, Fourth Hospital of HebeiMedical University, No. 12, Jiankang Road, Chang’an District, Shijiazhuang 050011, Hebei, China
推荐引用方式(GB/T 7714)：
Bai Tao,Cui Yanzhi,Yang Xian,et al.miR-302a-3p targets FMR1 to regulate pyroptosis of renal tubular epithelial cells induced by hypoxia/reoxygenation injury.[J].EXPERIMENTAL PHYSIOLOGY.2021,106(12):2531-2541.doi:10.1113/EP089887.
APA：
Bai Tao,Cui Yanzhi,Yang Xian,Cui Xinyue,Yan Congmin...&Dong Chunhui.(2021).miR-302a-3p targets FMR1 to regulate pyroptosis of renal tubular epithelial cells induced by hypoxia/reoxygenation injury..EXPERIMENTAL PHYSIOLOGY,106,(12)
MLA：
Bai Tao,et al."miR-302a-3p targets FMR1 to regulate pyroptosis of renal tubular epithelial cells induced by hypoxia/reoxygenation injury.".EXPERIMENTAL PHYSIOLOGY 106..12(2021):2531-2541
