TY - JOUR ID - 19488 TI - Hepatitis B virus X mediates podocyte pyroptosis by regulating the ROS/NLRP3 signaling pathway in hepatitis B virus-associated glomerulonephritis JO - Iranian Journal of Basic Medical Sciences JA - IJBMS LA - en SN - 2008-3866 AU - Yu, Yani AU - Dong, Hui AU - Sun, Jingyi AU - Li, Baoshuang AU - Chen, Yueqi AU - Feng, Moxuan AU - Yang, Xiaoqian AU - Jiang, Wei AD - Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao 266003, Shandong, China AD - Health Management Center, The Affiliated Hospital of Qingdao University, Qingdao 266003, Shandong, China Y1 - 2022 PY - 2022 VL - 25 IS - 1 SP - 103 EP - 109 KW - Glomerulonephritis KW - HBx KW - NLRP3 KW - Pyroptosis KW - ROS DO - 10.22038/ijbms.2022.61105.13520 N2 - Objective(s): This study was designed to investigate whether HBx-induced podocyte injury is related to the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome and the specific mechanism of the oxidative stress pathway in hepatitis B virus-associated glomerulonephritis (HBV-GN).Materials and Methods: The HBx gene was overexpressed in renal podocytes to mimic HBV-GN. Podocyte morphology was observed under a scanning electron microscope. Reactive oxygen species (ROS) generation was detected by dichlorodihydrofluorescein diacetate (DCFH-DA) assay. The podocytes in each group were treated with Hoechst 33342 and subjected to immunofluorescence staining. Caspase-1 activity and LDH levels were assessed with a Caspase-1 Activity Assay Kit and an LDH ELISA Kit, respectively. The expression of all pyroptosis-related proteins was examined by Western blot analysis.Results: Pyroptosis-related proteins, including NLRP3, apoptosis-associated speck-like protein containing card (ASC), caspase-1, IL-1β, and IL-18 (P<0.05), were up-regulated upon HBx overexpression, and caspase-1 enzyme activity and LDH and Desmin expression were also enhanced (P<0.05). NLRP3 knockdown attenuated the increased expression of pyroptosis-related proteins upon HBx overexpression (P<0.05), which was also achieved by the addition of an ROS inhibitor (P<0.05).Conclusion: HBx regulates podocyte pyroptosis in HBV-GN by targeting the NLRP3 inflammasome, and mitochondrial oxidative stress plays an important role in this process. UR - https://ijbms.mums.ac.ir/article_19488.html L1 - https://ijbms.mums.ac.ir/article_19488_92687f9c59c49971b7d4f4f034823b31.pdf ER -