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XIST Promote Calcium Oxalate Nephrocalcinosis Induced Renal Inflammatory and Oxidative Injury Via miR-223-NLRP3 Pathway

25 Pages Posted: 5 Feb 2021

See all articles by Peng Lv

Peng Lv

Chinese Academy of Sciences (CAS), Kunming Institute of Zoology, State Key Laboratory of Membrane Biology; Chinese Academy of Sciences (CAS) - Institute for Stem Cell and Regeneration; Chinese Academy of Sciences (CAS)

Haoran Liu

Huazhong University of Science and Technology - Department of Urology

Tao Ye

Huazhong University of Science and Technology - Department of Urology

Xiaoqi Yang

Huazhong University of Science and Technology - Department of Urology

Chen Duan

Huazhong University of Science and Technology - Department of Urology

Xiangyang Yao

Huazhong University of Science and Technology - Department of Urology

Bo Li

Huazhong University of Science and Technology - Department of Urology

Kun Tang

Huazhong University of Science and Technology - Department of Urology

Zhiqiang Chen

Huazhong University of Science and Technology - Department of Urology

Tao Wang

Xiamen University - Department of Urology

Yaoliang Deng

Guangxi Medical University - Department of Urology

Guohua Zeng

Guangzhou Medical University - Guangdong Provincial Key Laboratory of Urology

Jianhe Liu

Kunming Medical University - Department of Urology

Jinchun Xing

Xiamen University - Department of Urology Surgery

Zhangqun Ye

Huazhong University of Science and Technology - Tongji Hospital

Hua Xu

Huazhong University of Science and Technology - Department of Urology

More...

Abstract

Background: The function of lncRNA X‐inactive specific transcript (XIST) in many diseases, including cancers and inflammatory sickness, has been elucidated in previous papers. But for renal calculus, it remains poorly understood. In this study, we revealed the potential effects of XIST on kidney stones via inflammatory response and oxidative stress.

Method: We established a glyoxylate-induced calcium oxalate (CaOx) stone mouse model and exposed HK-2 cells to calcium oxalate monohydrate (COM). The interactions among XIST, miR-223 and NOD‐like receptor protein 3 (NLRP3) and respective effect were studied via the analysis of RNAs and protein expressions, luciferase activity, and immunohistochemistry (IHC). Necrosis and reactive oxygen species (ROS) generation were detected after XIST silence, miR-223 activation and inhibition or both of XIST knock-down and miR-223 activation in vitro and in vivo.

Finding: The levels of XIST, NLRP3, Caspase-1 and IL-1β were notably increased in the kidney samples from the glyoxylate-induced CaOx stone mouse model. XIST knockdown significantly suppressed the inflammatory damage and ROS production, and further attenuated kidney stones formation. MiRNA-223 mimics also exerted the same effects. Moreover, we verified the interactions among XIST, miRNA-223 and NLRP3 and the subsequent effects.

Interpretation: Our results suggested that lncRNA XIST participated in the formation and progression of renal calculus via interplaying with miR-223 and the NLRP3/Caspase-1/IL-1β pathway to mediate inflammatory response and ROS production. 

Funding: This study was supported by National Natural Science Foundation of China (8167031233).

Declaration of Interest: The authors declare that they have no competing conflicts of interest.

Ethical Approval: The animal study was approved by the Ethics Committee of Tongji Hospital.

Suggested Citation

Lv, Peng and Liu, Haoran and Ye, Tao and Yang, Xiaoqi and Duan, Chen and Yao, Xiangyang and Li, Bo and Tang, Kun and Chen, Zhiqiang and Wang, Tao and Deng, Yaoliang and Zeng, Guohua and Liu, Jianhe and Xing, Jinchun and Ye, Zhangqun and Xu, Hua, XIST Promote Calcium Oxalate Nephrocalcinosis Induced Renal Inflammatory and Oxidative Injury Via miR-223-NLRP3 Pathway. Available at SSRN: https://ssrn.com/abstract=3779874 or http://dx.doi.org/10.2139/ssrn.3779874

Peng Lv

Chinese Academy of Sciences (CAS), Kunming Institute of Zoology, State Key Laboratory of Membrane Biology

Beijing
China

Chinese Academy of Sciences (CAS) - Institute for Stem Cell and Regeneration

Beijing
China

Chinese Academy of Sciences (CAS)

Building 7, NO. 80 Zhongguancun Road
Beijing, Beijing 100190
China

Haoran Liu

Huazhong University of Science and Technology - Department of Urology

China

Tao Ye

Huazhong University of Science and Technology - Department of Urology

China

Xiaoqi Yang

Huazhong University of Science and Technology - Department of Urology

China

Chen Duan

Huazhong University of Science and Technology - Department of Urology ( email )

China

Xiangyang Yao

Huazhong University of Science and Technology - Department of Urology

China

Bo Li

Huazhong University of Science and Technology - Department of Urology

China

Kun Tang

Huazhong University of Science and Technology - Department of Urology ( email )

China

Zhiqiang Chen

Huazhong University of Science and Technology - Department of Urology ( email )

China

Tao Wang

Xiamen University - Department of Urology

Xiamen, 361003
China

Yaoliang Deng

Guangxi Medical University - Department of Urology ( email )

22 Shuangyong Rd
Qingxiu Qu, Nanning Shi
Guangxi Zhuangzuzizhiqu, 530021
China

Guohua Zeng

Guangzhou Medical University - Guangdong Provincial Key Laboratory of Urology ( email )

Guangzhou
China

Jianhe Liu

Kunming Medical University - Department of Urology

China

Jinchun Xing

Xiamen University - Department of Urology Surgery ( email )

Xiamen, Fujian 361003
China
(86)-05922139814 (Phone)

Zhangqun Ye

Huazhong University of Science and Technology - Tongji Hospital ( email )

1239 Siping Road
Shanghai, 200092
China

Hua Xu (Contact Author)

Huazhong University of Science and Technology - Department of Urology ( email )

China