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...
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| Format: | Article |
| Language: | English |
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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 |
| _version_ | 1819210480826187776 |
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| author | Yani Yu Hui Dong Jingyi Sun Baoshuang Li Yueqi Chen Moxuan Feng Xiaoqian Yang Wei Jiang |
| author_facet | Yani Yu Hui Dong Jingyi Sun Baoshuang Li Yueqi Chen Moxuan Feng Xiaoqian Yang Wei Jiang |
| author_sort | Yani Yu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-23T06:11:51Z |
| format | Article |
| id | doaj.art-bb9cdb1a579842dcba4d2c0160637c98 |
| institution | Directory Open Access Journal |
| issn | 2008-3866 2008-3874 |
| language | English |
| last_indexed | 2024-12-23T06:11:51Z |
| publishDate | 2022-01-01 |
| publisher | Mashhad University of Medical Sciences |
| record_format | Article |
| series | Iranian Journal of Basic Medical Sciences |
| spelling | doaj.art-bb9cdb1a579842dcba4d2c0160637c982022-12-21T17:57:26ZengMashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-38662008-38742022-01-0125110310910.22038/ijbms.2022.61105.1352019488Hepatitis B virus X mediates podocyte pyroptosis by regulating the ROS/NLRP3 signaling pathway in hepatitis B virus-associated glomerulonephritisYani Yu0Hui Dong1Jingyi Sun2Baoshuang Li3Yueqi Chen4Moxuan Feng5Xiaoqian Yang6Wei Jiang7Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao 266003, Shandong, ChinaHealth Management Center, The Affiliated Hospital of Qingdao University, Qingdao 266003, Shandong, ChinaDepartment of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao 266003, Shandong, ChinaDepartment of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao 266003, Shandong, ChinaDepartment of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao 266003, Shandong, ChinaDepartment of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao 266003, Shandong, ChinaDepartment of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao 266003, Shandong, ChinaDepartment of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao 266003, Shandong, ChinaObjective(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.https://ijbms.mums.ac.ir/article_19488_92687f9c59c49971b7d4f4f034823b31.pdfglomerulonephritishbxnlrp3pyroptosisros |
| spellingShingle | Yani Yu Hui Dong Jingyi Sun Baoshuang Li Yueqi Chen Moxuan Feng Xiaoqian Yang Wei Jiang Hepatitis B virus X mediates podocyte pyroptosis by regulating the ROS/NLRP3 signaling pathway in hepatitis B virus-associated glomerulonephritis Iranian Journal of Basic Medical Sciences glomerulonephritis hbx nlrp3 pyroptosis ros |
| title | Hepatitis B virus X mediates podocyte pyroptosis by regulating the ROS/NLRP3 signaling pathway in hepatitis B virus-associated glomerulonephritis |
| title_full | Hepatitis B virus X mediates podocyte pyroptosis by regulating the ROS/NLRP3 signaling pathway in hepatitis B virus-associated glomerulonephritis |
| title_fullStr | Hepatitis B virus X mediates podocyte pyroptosis by regulating the ROS/NLRP3 signaling pathway in hepatitis B virus-associated glomerulonephritis |
| title_full_unstemmed | Hepatitis B virus X mediates podocyte pyroptosis by regulating the ROS/NLRP3 signaling pathway in hepatitis B virus-associated glomerulonephritis |
| title_short | Hepatitis B virus X mediates podocyte pyroptosis by regulating the ROS/NLRP3 signaling pathway in hepatitis B virus-associated glomerulonephritis |
| title_sort | hepatitis b virus x mediates podocyte pyroptosis by regulating the ros nlrp3 signaling pathway in hepatitis b virus associated glomerulonephritis |
| topic | glomerulonephritis hbx nlrp3 pyroptosis ros |
| url | https://ijbms.mums.ac.ir/article_19488_92687f9c59c49971b7d4f4f034823b31.pdf |
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