Open AccessXIST Inhibition Attenuates Calcium Oxalate Nephrocalcinosis-Induced Renal Inflammation and Oxidative Injury via the miR-223/NLRP3 Pathway
Author(s) -
Ping Lv,
Haoran Liu,
Ye Tao,
Xiaoqi Yang,
Chaojun Duan,
Xiangyang Yao,
Bo Li,
Kun Tang,
Zhiqiang Chen,
Jianhe Liu,
Yaoliang Deng,
Tao Wang,
Jinchun Xing,
Chaozhao Liang,
Hua Xu,
Zhangqun Ye
Publication year - 2021
Publication title -
oxidative medicine and cellular longevity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.494
H-Index - 93
eISSN - 1942-0900
pISSN - 1942-0994
DOI - 10.1155/2021/1676152
Subject(s) - xist , gene knockdown , inflammation , oxidative stress , chemistry , microbiology and biotechnology , calcium oxalate , kidney , biology , cancer research , oxalate , apoptosis , endocrinology , biochemistry , immunology , x inactivation , x chromosome , organic chemistry , gene
The roles of the lncRNA X inactive specific transcript (XIST) in many diseases, including cancers and inflammatory sickness, have been previously elucidated. However, renal calculus remained poorly understood. In this study, we revealed the potential effects of XIST on kidney stones that were exerted via inflammatory response and oxidative stress mechanisms. 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-223-3p, and NOD-like receptor protein 3 (NLRP3) and their respective effects were determined by RNAs and protein expression, luciferase activity, and immunohistochemistry (IHC) assays. Cell necrosis, reactive oxygen species (ROS) generation, and inflammatory responses were detected after silencing XIST, activating and inhibiting miR-223-3p, and both knocking down XIST and activating miR-223-3p in vitro and in vivo. The XIST, NLRP3, caspase-1, and IL-1 β levels were notably increased in kidney samples from glyoxylate-induced CaOx stone model mice. XIST knockdown significantly suppressed the inflammatory damage and ROS production and further attenuated oxalate crystal deposition. miRNA-223-3p mimics also exerted the same effects. Moreover, we verified the interactions among XIST, miRNA-223-3p and NLRP3, and the subsequent effects. Our results suggest that the lncRNA XIST participates in the formation and progression of renal calculus by interacting with miR-223-3p and the NLRP3/Caspase-1/IL-1 β pathway to mediate the inflammatory response and ROS production.