SAA3 deficiency exacerbates intestinal fibrosis in DSS-induced IBD mouse model
Abstract Intestinal fibrosis, as a late-stage complication of inflammatory bowel disease (IBD), leads to bowel obstruction and requires surgical intervention, significantly lowering the quality of life of affected patients. SAA3, a highly conserved member of the serum amyloid A (SAA) apolipoprotein...
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-01-01
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| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-025-02299-x |
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| author | Xiaodong Zou Tong Wu Jianjiao Lin Tao Su Hui Xiao Chuyan Ni Lijuan Hu Wenchu Lin Weilin Chen Richard D. Ye Li Xiang |
| author_facet | Xiaodong Zou Tong Wu Jianjiao Lin Tao Su Hui Xiao Chuyan Ni Lijuan Hu Wenchu Lin Weilin Chen Richard D. Ye Li Xiang |
| author_sort | Xiaodong Zou |
| collection | DOAJ |
| description | Abstract Intestinal fibrosis, as a late-stage complication of inflammatory bowel disease (IBD), leads to bowel obstruction and requires surgical intervention, significantly lowering the quality of life of affected patients. SAA3, a highly conserved member of the serum amyloid A (SAA) apolipoprotein family in mice, is synthesized primarily as an acute phase reactant in response to infection, inflammation and trauma. An increasing number of evidence suggests that SAA3 exerts a vital role in the fibrotic process, even though the underlying mechanisms are not yet fully comprehended. This study utilized dextran sulfate sodium (DSS) to establish an IBD mouse model and observed that the SAA3-deficient mice exhibited more severe intestinal fibrosis. Our results further indicated that SAA3 genetic disruption in fibroblasts enhanced cell activation to myofibroblasts through HSPB1/NF-κB/TGF-β1/Smads signaling cascade, exacerbating the pathological phenotype of intestinal fibrosis. Collectively, our results shed novel lights on regulating SAA3 in intestinal fibrosis and indicate the potential to develop therapeutic strategies for IBD patients. |
| format | Article |
| id | doaj-art-5f24ec28927645eb8045751c3f96fe3f |
| institution | Kabale University |
| issn | 2058-7716 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death Discovery |
| spelling | doaj-art-5f24ec28927645eb8045751c3f96fe3f2025-01-26T12:15:28ZengNature Publishing GroupCell Death Discovery2058-77162025-01-0111111010.1038/s41420-025-02299-xSAA3 deficiency exacerbates intestinal fibrosis in DSS-induced IBD mouse modelXiaodong Zou0Tong Wu1Jianjiao Lin2Tao Su3Hui Xiao4Chuyan Ni5Lijuan Hu6Wenchu Lin7Weilin Chen8Richard D. Ye9Li Xiang10Department of Gastroenterology, The Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Shenzhen & Longgang District People’s Hospital of ShenzhenKobilka Institute of Innovative Drug Discovery, School of Medicine, The Chinese University of Hong KongDepartment of Gastroenterology, The Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Shenzhen & Longgang District People’s Hospital of ShenzhenDepartment of Gastroenterology, The Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Shenzhen & Longgang District People’s Hospital of ShenzhenDepartment of Pathology, The Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Shenzhen & Longgang District People’s Hospital of ShenzhenDepartment of Gastroenterology, The Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Shenzhen & Longgang District People’s Hospital of ShenzhenDepartment of Gastroenterology, The Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Shenzhen & Longgang District People’s Hospital of ShenzhenInstitute of Digestive Disease, The Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Shenzhen & Longgang District People’s Hospital of ShenzhenMarshall Laboratory of Biomedical Engineering, Institute of Biological Therapy, Shenzhen University Medical School, Shenzhen UniversityKobilka Institute of Innovative Drug Discovery, School of Medicine, The Chinese University of Hong KongDepartment of Gastroenterology, The Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Shenzhen & Longgang District People’s Hospital of ShenzhenAbstract Intestinal fibrosis, as a late-stage complication of inflammatory bowel disease (IBD), leads to bowel obstruction and requires surgical intervention, significantly lowering the quality of life of affected patients. SAA3, a highly conserved member of the serum amyloid A (SAA) apolipoprotein family in mice, is synthesized primarily as an acute phase reactant in response to infection, inflammation and trauma. An increasing number of evidence suggests that SAA3 exerts a vital role in the fibrotic process, even though the underlying mechanisms are not yet fully comprehended. This study utilized dextran sulfate sodium (DSS) to establish an IBD mouse model and observed that the SAA3-deficient mice exhibited more severe intestinal fibrosis. Our results further indicated that SAA3 genetic disruption in fibroblasts enhanced cell activation to myofibroblasts through HSPB1/NF-κB/TGF-β1/Smads signaling cascade, exacerbating the pathological phenotype of intestinal fibrosis. Collectively, our results shed novel lights on regulating SAA3 in intestinal fibrosis and indicate the potential to develop therapeutic strategies for IBD patients.https://doi.org/10.1038/s41420-025-02299-x |
| spellingShingle | Xiaodong Zou Tong Wu Jianjiao Lin Tao Su Hui Xiao Chuyan Ni Lijuan Hu Wenchu Lin Weilin Chen Richard D. Ye Li Xiang SAA3 deficiency exacerbates intestinal fibrosis in DSS-induced IBD mouse model Cell Death Discovery |
| title | SAA3 deficiency exacerbates intestinal fibrosis in DSS-induced IBD mouse model |
| title_full | SAA3 deficiency exacerbates intestinal fibrosis in DSS-induced IBD mouse model |
| title_fullStr | SAA3 deficiency exacerbates intestinal fibrosis in DSS-induced IBD mouse model |
| title_full_unstemmed | SAA3 deficiency exacerbates intestinal fibrosis in DSS-induced IBD mouse model |
| title_short | SAA3 deficiency exacerbates intestinal fibrosis in DSS-induced IBD mouse model |
| title_sort | saa3 deficiency exacerbates intestinal fibrosis in dss induced ibd mouse model |
| url | https://doi.org/10.1038/s41420-025-02299-x |
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