Hepatitis B virus X mediates podocyte pyroptosis by regulating the ROS/NLRP3 signaling pathway in hepatitis B virus-associated glomerulonephritis
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 glomerulonephri...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Mashhad University of Medical Sciences
2022-01-01
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| Series: | Iranian Journal of Basic Medical Sciences |
| Subjects: | |
| Online Access: | https://ijbms.mums.ac.ir/article_19488_92687f9c59c49971b7d4f4f034823b31.pdf |
| Summary: | 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. |
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| ISSN: | 2008-3866 2008-3874 |