Caspase-11–Mediated Hepatocytic Pyroptosis Promotes the Progression of Nonalcoholic SteatohepatitisSummary
Background: Nonalcoholic steatohepatitis (NASH) is an inflammatory disease with severe outcomes. Hepatocyte death, including apoptosis, necrosis, and pyroptosis, has been implicated in pathophysiology of NASH. Pyroptosis is mediated by inflammasome activation pathways including caspase-1–mediated ca...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-01-01
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| Series: | Cellular and Molecular Gastroenterology and Hepatology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352345X21000801 |
| _version_ | 1818354436995547136 |
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| author | Yingwei Zhu Han Zhao Jian Lu Kai Lin Jingbin Ni Gaojue Wu Hong Tang |
| author_facet | Yingwei Zhu Han Zhao Jian Lu Kai Lin Jingbin Ni Gaojue Wu Hong Tang |
| author_sort | Yingwei Zhu |
| collection | DOAJ |
| description | Background: Nonalcoholic steatohepatitis (NASH) is an inflammatory disease with severe outcomes. Hepatocyte death, including apoptosis, necrosis, and pyroptosis, has been implicated in pathophysiology of NASH. Pyroptosis is mediated by inflammasome activation pathways including caspase-1–mediated canonical signaling pathway and caspase-11–mediated noncanonical signaling pathway. Until now, the precise role of caspase-11 in NASH remains unknown. In the present study, the potential roles of caspase-11 in NASH were explored. Methods: We established methionine- and choline-deficient diet (MCD)–induced NASH mice model using wild-type caspase-11–deficient mice. The expression of caspase-11, liver injury, fibrosis, inflammation, and activation of gasdermin D and interleukin-1β were evaluated. Results: Upregulated caspase-11 was detected in liver of mice with NASH. MCD-treated caspase-11–deficient mice had significantly decreased liver injury, fibrosis, and inflammation. The activation of gasdermin D and interleukin-1β was inhibited in caspase-11–deficient mice after MCD treatment. Overexpression of caspase-11 promoted steatohepatitis. Conclusions: Caspase-11–mediated hepatocytic pyroptosis promotes the progression of NASH. |
| first_indexed | 2024-12-13T19:25:24Z |
| format | Article |
| id | doaj.art-747390e134454358b2ac4e3b07564d41 |
| institution | Directory Open Access Journal |
| issn | 2352-345X |
| language | English |
| last_indexed | 2024-12-13T19:25:24Z |
| publishDate | 2021-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cellular and Molecular Gastroenterology and Hepatology |
| spelling | doaj.art-747390e134454358b2ac4e3b07564d412022-12-21T23:34:03ZengElsevierCellular and Molecular Gastroenterology and Hepatology2352-345X2021-01-01122653664Caspase-11–Mediated Hepatocytic Pyroptosis Promotes the Progression of Nonalcoholic SteatohepatitisSummaryYingwei Zhu0Han Zhao1Jian Lu2Kai Lin3Jingbin Ni4Gaojue Wu5Hong Tang6Department of Gastroenterology, Wuxi No. 2 People’s Hospital, Affiliated Wuxi Clinical College of Nantong University, Wuxi, China; Department of Gastroenterology, Affiliated Wuxi No. 2 People’s Hospital of Nanjing Medical University, Wuxi, ChinaDepartment of Gastroenterology, Affiliated Wuxi No. 2 People’s Hospital of Nanjing Medical University, Wuxi, ChinaDepartment of Gastroenterology, Affiliated Wuxi No. 2 People’s Hospital of Nanjing Medical University, Wuxi, ChinaDepartment of Gastroenterology, Affiliated Wuxi No. 2 People’s Hospital of Nanjing Medical University, Wuxi, ChinaDepartment of Gastroenterology, Affiliated Wuxi No. 2 People’s Hospital of Nanjing Medical University, Wuxi, ChinaDepartment of Gastroenterology, Wuxi No. 2 People’s Hospital, Affiliated Wuxi Clinical College of Nantong University, Wuxi, China; Department of Gastroenterology, Affiliated Wuxi No. 2 People’s Hospital of Nanjing Medical University, Wuxi, China; Correspondence Address correspondence to: Gaojue Wu, MD, Department of Gastroenterology, Wuxi No.2 People’s Hospital, Affiliated Wuxi Clinical College of Nantong University, No. 68 Zhongshan Road, Wuxi 214002, Jiangsu, China. fax: 86-13914118290Department of Pathology, Affiliated Wuxi No.2 People’s Hospital of Nanjing Medical University, Wuxi, China; Hong Tang, BS, Department of Pathology, the Affiliated Wuxi No.2 People’s Hospital of Nanjing Medical University, No. 68 Zhongshan Road, Wuxi 214002, Jiangsu, China. fax: 86-510-68562222-6470Background: Nonalcoholic steatohepatitis (NASH) is an inflammatory disease with severe outcomes. Hepatocyte death, including apoptosis, necrosis, and pyroptosis, has been implicated in pathophysiology of NASH. Pyroptosis is mediated by inflammasome activation pathways including caspase-1–mediated canonical signaling pathway and caspase-11–mediated noncanonical signaling pathway. Until now, the precise role of caspase-11 in NASH remains unknown. In the present study, the potential roles of caspase-11 in NASH were explored. Methods: We established methionine- and choline-deficient diet (MCD)–induced NASH mice model using wild-type caspase-11–deficient mice. The expression of caspase-11, liver injury, fibrosis, inflammation, and activation of gasdermin D and interleukin-1β were evaluated. Results: Upregulated caspase-11 was detected in liver of mice with NASH. MCD-treated caspase-11–deficient mice had significantly decreased liver injury, fibrosis, and inflammation. The activation of gasdermin D and interleukin-1β was inhibited in caspase-11–deficient mice after MCD treatment. Overexpression of caspase-11 promoted steatohepatitis. Conclusions: Caspase-11–mediated hepatocytic pyroptosis promotes the progression of NASH.http://www.sciencedirect.com/science/article/pii/S2352345X21000801Caspase-11PyroptosisLiverNonalcoholic Steatohepatitis |
| spellingShingle | Yingwei Zhu Han Zhao Jian Lu Kai Lin Jingbin Ni Gaojue Wu Hong Tang Caspase-11–Mediated Hepatocytic Pyroptosis Promotes the Progression of Nonalcoholic SteatohepatitisSummary Cellular and Molecular Gastroenterology and Hepatology Caspase-11 Pyroptosis Liver Nonalcoholic Steatohepatitis |
| title | Caspase-11–Mediated Hepatocytic Pyroptosis Promotes the Progression of Nonalcoholic SteatohepatitisSummary |
| title_full | Caspase-11–Mediated Hepatocytic Pyroptosis Promotes the Progression of Nonalcoholic SteatohepatitisSummary |
| title_fullStr | Caspase-11–Mediated Hepatocytic Pyroptosis Promotes the Progression of Nonalcoholic SteatohepatitisSummary |
| title_full_unstemmed | Caspase-11–Mediated Hepatocytic Pyroptosis Promotes the Progression of Nonalcoholic SteatohepatitisSummary |
| title_short | Caspase-11–Mediated Hepatocytic Pyroptosis Promotes the Progression of Nonalcoholic SteatohepatitisSummary |
| title_sort | caspase 11 mediated hepatocytic pyroptosis promotes the progression of nonalcoholic steatohepatitissummary |
| topic | Caspase-11 Pyroptosis Liver Nonalcoholic Steatohepatitis |
| url | http://www.sciencedirect.com/science/article/pii/S2352345X21000801 |
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