USP50 regulates NLRP3 inflammasome activation in duodenogastric reflux-induced gastric tumorigenesis
Duodenogastric reflux (DGR) has been linked to the onset of gastric cancer (GC), although the precise mechanism is yet obscure. Herein, we aimed to investigate how refluxed bile acids (BAs) and macrophages are involved in gastric carcinogenesis. In both active human bile reflux gastritis and the mur...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-02-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1326137/full |
| _version_ | 1797295236875026432 |
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| author | Chenye Zhao Mingchao Mu Xiaopeng Li Zepeng Dong Jiahao Wang Chengzhi Yao Jianbao Zheng Xuejun Sun Junhui Yu |
| author_facet | Chenye Zhao Mingchao Mu Xiaopeng Li Zepeng Dong Jiahao Wang Chengzhi Yao Jianbao Zheng Xuejun Sun Junhui Yu |
| author_sort | Chenye Zhao |
| collection | DOAJ |
| description | Duodenogastric reflux (DGR) has been linked to the onset of gastric cancer (GC), although the precise mechanism is yet obscure. Herein, we aimed to investigate how refluxed bile acids (BAs) and macrophages are involved in gastric carcinogenesis. In both active human bile reflux gastritis and the murine DGR model, ubiquitin specific protease 50 (USP50) was dramatically raised, and macrophages were the principal leukocyte subset that upregulated USP50 expression. Enhancing USP50 expression amplified bile acid-induced NLR family pyrin domain containing 3 (NLRP3) inflammasome activation and subsequent high-mobility group box protein 1 (HMGB1) release, while USP50 deficiency resulted in the reversed alteration. Mechanistically, USP50 interacted with and deubiquitinated apoptosis-associated speck-like protein containing CARD (ASC) to activate NLRP3 inflammasome. The release of HMGB1 contributes to gastric tumorigenesis by PI3K/AKT and MAPK/ERK pathways. These results may provide new insights into bile reflux-related gastric carcinogenesis and options for the prevention of DGR-associated GC. |
| first_indexed | 2024-03-07T21:43:50Z |
| format | Article |
| id | doaj.art-c738cef0834c49bb87e16f5ca7fbb64e |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-07T21:43:50Z |
| publishDate | 2024-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-c738cef0834c49bb87e16f5ca7fbb64e2024-02-26T04:32:57ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-02-011510.3389/fimmu.2024.13261371326137USP50 regulates NLRP3 inflammasome activation in duodenogastric reflux-induced gastric tumorigenesisChenye ZhaoMingchao MuXiaopeng LiZepeng DongJiahao WangChengzhi YaoJianbao ZhengXuejun SunJunhui YuDuodenogastric reflux (DGR) has been linked to the onset of gastric cancer (GC), although the precise mechanism is yet obscure. Herein, we aimed to investigate how refluxed bile acids (BAs) and macrophages are involved in gastric carcinogenesis. In both active human bile reflux gastritis and the murine DGR model, ubiquitin specific protease 50 (USP50) was dramatically raised, and macrophages were the principal leukocyte subset that upregulated USP50 expression. Enhancing USP50 expression amplified bile acid-induced NLR family pyrin domain containing 3 (NLRP3) inflammasome activation and subsequent high-mobility group box protein 1 (HMGB1) release, while USP50 deficiency resulted in the reversed alteration. Mechanistically, USP50 interacted with and deubiquitinated apoptosis-associated speck-like protein containing CARD (ASC) to activate NLRP3 inflammasome. The release of HMGB1 contributes to gastric tumorigenesis by PI3K/AKT and MAPK/ERK pathways. These results may provide new insights into bile reflux-related gastric carcinogenesis and options for the prevention of DGR-associated GC.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1326137/fullUSP50gastric tumorigenesisNLRP3 inflammasomepyroptosisHMGB1 |
| spellingShingle | Chenye Zhao Mingchao Mu Xiaopeng Li Zepeng Dong Jiahao Wang Chengzhi Yao Jianbao Zheng Xuejun Sun Junhui Yu USP50 regulates NLRP3 inflammasome activation in duodenogastric reflux-induced gastric tumorigenesis Frontiers in Immunology USP50 gastric tumorigenesis NLRP3 inflammasome pyroptosis HMGB1 |
| title | USP50 regulates NLRP3 inflammasome activation in duodenogastric reflux-induced gastric tumorigenesis |
| title_full | USP50 regulates NLRP3 inflammasome activation in duodenogastric reflux-induced gastric tumorigenesis |
| title_fullStr | USP50 regulates NLRP3 inflammasome activation in duodenogastric reflux-induced gastric tumorigenesis |
| title_full_unstemmed | USP50 regulates NLRP3 inflammasome activation in duodenogastric reflux-induced gastric tumorigenesis |
| title_short | USP50 regulates NLRP3 inflammasome activation in duodenogastric reflux-induced gastric tumorigenesis |
| title_sort | usp50 regulates nlrp3 inflammasome activation in duodenogastric reflux induced gastric tumorigenesis |
| topic | USP50 gastric tumorigenesis NLRP3 inflammasome pyroptosis HMGB1 |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1326137/full |
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