SaaS sRNA promotes the interfering effect of Salmonella on hepatic iron metabolism via modulating ferroportin 1
Summary: Iron limitation plays a fundamental role in host immunity against Salmonella infection. The mechanisms by which Salmonella antagonizes nutritional immunity, particularly those regulated by small non-coding RNAs (sRNAs), remain incompletely understood. In this study, we investigated the role...
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Elsevier
2025-02-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004224028876 |
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| author | Linlin Cai Yunting Xie Haijing Hu Chongyang Lv Liangting Shao Huhu Wang Xinglian Xu Guanghong Zhou |
| author_facet | Linlin Cai Yunting Xie Haijing Hu Chongyang Lv Liangting Shao Huhu Wang Xinglian Xu Guanghong Zhou |
| author_sort | Linlin Cai |
| collection | DOAJ |
| description | Summary: Iron limitation plays a fundamental role in host immunity against Salmonella infection. The mechanisms by which Salmonella antagonizes nutritional immunity, particularly those regulated by small non-coding RNAs (sRNAs), remain incompletely understood. In this study, we investigated the role of a previously identified sRNA, Salmonella adhesive-associated sRNA (SaaS), in host iron metabolism. Utilizing a combined BALB/c mouse model and HepG2 cell model, we demonstrated that SaaS enhances hepcidin synthesis via the bone morphogenetic protein (BMP)-SMAD pathway, leading to decreased ferroportin 1 level. This suppression of ferroportin 1 results in reduced serum iron and increased hepatic iron accumulation, ultimately causing iron-deficiency anemia. The accumulation of iron triggers hepatic oxidative stress, exacerbating liver damage. Concurrently, SaaS activates the signal transducer and activator of transcription 3 (STAT3) pathway in a triggering receptor expressed on myeloid cells-1 (TREM1)-interleukin (IL)-6-dependent manner, intensifying the inflammatory response. Collectively, these results provide evidence that sRNAs serve as crucial regulators of Salmonella pathogenesis and underscore the potential of targeting sRNAs for the prevention of salmonellosis. |
| format | Article |
| id | doaj-art-15295bf803664910bcf4b67acca592e9 |
| institution | Kabale University |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-15295bf803664910bcf4b67acca592e92025-01-29T05:01:37ZengElsevieriScience2589-00422025-02-01282111660SaaS sRNA promotes the interfering effect of Salmonella on hepatic iron metabolism via modulating ferroportin 1Linlin Cai0Yunting Xie1Haijing Hu2Chongyang Lv3Liangting Shao4Huhu Wang5Xinglian Xu6Guanghong Zhou7Key Laboratory of Meat Processing (Ministry of Agriculture), State Key Lab of Meat Quality Control and Cultured Meat Development (Ministry of Science and Technology), Jiangsu Collaborative Innovation Center of Meat Production and Processing, College of Food Science and Technology, Nanjing Agricultural University, Nanjing, Jiangsu 210095, P.R. ChinaKey Laboratory of Meat Processing (Ministry of Agriculture), State Key Lab of Meat Quality Control and Cultured Meat Development (Ministry of Science and Technology), Jiangsu Collaborative Innovation Center of Meat Production and Processing, College of Food Science and Technology, Nanjing Agricultural University, Nanjing, Jiangsu 210095, P.R. ChinaKey Laboratory of Meat Processing (Ministry of Agriculture), State Key Lab of Meat Quality Control and Cultured Meat Development (Ministry of Science and Technology), Jiangsu Collaborative Innovation Center of Meat Production and Processing, College of Food Science and Technology, Nanjing Agricultural University, Nanjing, Jiangsu 210095, P.R. ChinaKey Laboratory of Meat Processing (Ministry of Agriculture), State Key Lab of Meat Quality Control and Cultured Meat Development (Ministry of Science and Technology), Jiangsu Collaborative Innovation Center of Meat Production and Processing, College of Food Science and Technology, Nanjing Agricultural University, Nanjing, Jiangsu 210095, P.R. ChinaKey Laboratory of Meat Processing (Ministry of Agriculture), State Key Lab of Meat Quality Control and Cultured Meat Development (Ministry of Science and Technology), Jiangsu Collaborative Innovation Center of Meat Production and Processing, College of Food Science and Technology, Nanjing Agricultural University, Nanjing, Jiangsu 210095, P.R. ChinaKey Laboratory of Meat Processing (Ministry of Agriculture), State Key Lab of Meat Quality Control and Cultured Meat Development (Ministry of Science and Technology), Jiangsu Collaborative Innovation Center of Meat Production and Processing, College of Food Science and Technology, Nanjing Agricultural University, Nanjing, Jiangsu 210095, P.R. China; Xinjiang Agricultural University, Urumqi, Xinjiang 830052, P.R. China; Corresponding authorKey Laboratory of Meat Processing (Ministry of Agriculture), State Key Lab of Meat Quality Control and Cultured Meat Development (Ministry of Science and Technology), Jiangsu Collaborative Innovation Center of Meat Production and Processing, College of Food Science and Technology, Nanjing Agricultural University, Nanjing, Jiangsu 210095, P.R. China; Corresponding authorKey Laboratory of Meat Processing (Ministry of Agriculture), State Key Lab of Meat Quality Control and Cultured Meat Development (Ministry of Science and Technology), Jiangsu Collaborative Innovation Center of Meat Production and Processing, College of Food Science and Technology, Nanjing Agricultural University, Nanjing, Jiangsu 210095, P.R. ChinaSummary: Iron limitation plays a fundamental role in host immunity against Salmonella infection. The mechanisms by which Salmonella antagonizes nutritional immunity, particularly those regulated by small non-coding RNAs (sRNAs), remain incompletely understood. In this study, we investigated the role of a previously identified sRNA, Salmonella adhesive-associated sRNA (SaaS), in host iron metabolism. Utilizing a combined BALB/c mouse model and HepG2 cell model, we demonstrated that SaaS enhances hepcidin synthesis via the bone morphogenetic protein (BMP)-SMAD pathway, leading to decreased ferroportin 1 level. This suppression of ferroportin 1 results in reduced serum iron and increased hepatic iron accumulation, ultimately causing iron-deficiency anemia. The accumulation of iron triggers hepatic oxidative stress, exacerbating liver damage. Concurrently, SaaS activates the signal transducer and activator of transcription 3 (STAT3) pathway in a triggering receptor expressed on myeloid cells-1 (TREM1)-interleukin (IL)-6-dependent manner, intensifying the inflammatory response. Collectively, these results provide evidence that sRNAs serve as crucial regulators of Salmonella pathogenesis and underscore the potential of targeting sRNAs for the prevention of salmonellosis.http://www.sciencedirect.com/science/article/pii/S2589004224028876immunologymicrobiology |
| spellingShingle | Linlin Cai Yunting Xie Haijing Hu Chongyang Lv Liangting Shao Huhu Wang Xinglian Xu Guanghong Zhou SaaS sRNA promotes the interfering effect of Salmonella on hepatic iron metabolism via modulating ferroportin 1 iScience immunology microbiology |
| title | SaaS sRNA promotes the interfering effect of Salmonella on hepatic iron metabolism via modulating ferroportin 1 |
| title_full | SaaS sRNA promotes the interfering effect of Salmonella on hepatic iron metabolism via modulating ferroportin 1 |
| title_fullStr | SaaS sRNA promotes the interfering effect of Salmonella on hepatic iron metabolism via modulating ferroportin 1 |
| title_full_unstemmed | SaaS sRNA promotes the interfering effect of Salmonella on hepatic iron metabolism via modulating ferroportin 1 |
| title_short | SaaS sRNA promotes the interfering effect of Salmonella on hepatic iron metabolism via modulating ferroportin 1 |
| title_sort | saas srna promotes the interfering effect of salmonella on hepatic iron metabolism via modulating ferroportin 1 |
| topic | immunology microbiology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004224028876 |
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