The deficiency of chymase mast cell protease 4 exacerbates dextran sulfate sodium salt-induced colitis in mice and is associated with altered microbiota and metabolome profiles
IntroductionUlcerative colitis (UC) is a chronic gastrointestinal disease characterized by symptoms of abdominal pain and diarrhea. Chymase is a serine protease released by the mast cells and is highly expressed in patients with UC. However, its role in disease pathogenesis remains poorly understoo...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-07-01
|
| Series: | Frontiers in Cellular and Infection Microbiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2025.1481927/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849702479997960192 |
|---|---|
| author | Zhiqiang Li Zhiqiang Li Zhiqiang Li Xiaoyuan Kuang Dashuang Mo Magnus Åbrink Ge Shan Jin-ping Li Can Yang Yuexi Wang Tao Shen Weiwei Yu |
| author_facet | Zhiqiang Li Zhiqiang Li Zhiqiang Li Xiaoyuan Kuang Dashuang Mo Magnus Åbrink Ge Shan Jin-ping Li Can Yang Yuexi Wang Tao Shen Weiwei Yu |
| author_sort | Zhiqiang Li |
| collection | DOAJ |
| description | IntroductionUlcerative colitis (UC) is a chronic gastrointestinal disease characterized by symptoms of abdominal pain and diarrhea. Chymase is a serine protease released by the mast cells and is highly expressed in patients with UC. However, its role in disease pathogenesis remains poorly understood. In mice, mast cell protease-4 (MCP-4) is considered as the functional homolog of human chymase, sharing similar enzymatic activity and biological roles.MethodsTo investigate the role of MCP-4 in UC, we induced colitis in Mcpt-4-deficient (Mcpt-4∆Cre) and littermate control (Mcpt-4fl/fl) mice using 2% dextran sulfate sodium salt (DSS) for 8 days followed by 2 days of water. After sacrifice, colon length was measured, and tissue samples were analyzed by histology (H&E and toluidine blue staining), qPCR, and protein assays. Colonic contents were collected for microbiota and metabolomics analysis.ResultsThe results show that the Mcpt-4-deficiency exacerbated colitis, as reflected by the significantly greater weight loss, higher histological scores, elevated levels of myeloperoxidase and most of determined cytokines. Furthermore, the Mcpt-4∆Cre colitis mice displayed a distinct shift in colonic microbiota composition, notably with significantly increased abundance of bacteria (Akkermansia and Turicibacter), associated with potentially worsened inflammation in colitis models. In addition, metabolomic profiling revealed alterations in colonic metabolites involved in key Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, including NF-kappa B signaling, Th1 and Th2 cell differentiation.DiscussionThese findings reveal that the mouse chymase MCPT-4 plays important roles in maintaining the intestinal homeostasis during colitis, potentially through regulation of colonic cytokines, microbial and metabolic networks. |
| format | Article |
| id | doaj-art-c166fa57d22d40c4b411b6dd75ee773f |
| institution | DOAJ |
| issn | 2235-2988 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj-art-c166fa57d22d40c4b411b6dd75ee773f2025-08-20T03:17:39ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882025-07-011510.3389/fcimb.2025.14819271481927The deficiency of chymase mast cell protease 4 exacerbates dextran sulfate sodium salt-induced colitis in mice and is associated with altered microbiota and metabolome profilesZhiqiang Li0Zhiqiang Li1Zhiqiang Li2Xiaoyuan Kuang3Dashuang Mo4Magnus Åbrink5Ge Shan6Jin-ping Li7Can Yang8Yuexi Wang9Tao Shen10Weiwei Yu11Department of Immunology, College of Basic Medicine, Guizhou Medical University, Guiyang, ChinaThe Key and Characteristic Laboratory of Modern Pathogen Biology, College of Basic Medicine, Guizhou Medical University; Department of Medical Parasitology, College of Basic Medicine, Guizhou Medical University, Guiyang, ChinaDepartment of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, SwedenThe Key and Characteristic Laboratory of Modern Pathogen Biology, College of Basic Medicine, Guizhou Medical University; Department of Medical Parasitology, College of Basic Medicine, Guizhou Medical University, Guiyang, ChinaDepartment of Immunology, College of Basic Medicine, Guizhou Medical University, Guiyang, ChinaDivision of Anatomy, Physiology, Immunology and Patholog, Department of Animal Biosciences, Swedish University of Agricultural Sciences, Uppsala, SwedenDepartment of Immunology, College of Basic Medicine, Guizhou Medical University, Guiyang, ChinaDepartment of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, SwedenUrologic Surgery Clinic, Tongren Municipal People’s Hospital, Tongren, ChinaDepartment of Immunology, College of Basic Medicine, Guizhou Medical University, Guiyang, ChinaDepartment of Immunology, College of Basic Medicine, Guizhou Medical University, Guiyang, ChinaDepartment of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, ChinaIntroductionUlcerative colitis (UC) is a chronic gastrointestinal disease characterized by symptoms of abdominal pain and diarrhea. Chymase is a serine protease released by the mast cells and is highly expressed in patients with UC. However, its role in disease pathogenesis remains poorly understood. In mice, mast cell protease-4 (MCP-4) is considered as the functional homolog of human chymase, sharing similar enzymatic activity and biological roles.MethodsTo investigate the role of MCP-4 in UC, we induced colitis in Mcpt-4-deficient (Mcpt-4∆Cre) and littermate control (Mcpt-4fl/fl) mice using 2% dextran sulfate sodium salt (DSS) for 8 days followed by 2 days of water. After sacrifice, colon length was measured, and tissue samples were analyzed by histology (H&E and toluidine blue staining), qPCR, and protein assays. Colonic contents were collected for microbiota and metabolomics analysis.ResultsThe results show that the Mcpt-4-deficiency exacerbated colitis, as reflected by the significantly greater weight loss, higher histological scores, elevated levels of myeloperoxidase and most of determined cytokines. Furthermore, the Mcpt-4∆Cre colitis mice displayed a distinct shift in colonic microbiota composition, notably with significantly increased abundance of bacteria (Akkermansia and Turicibacter), associated with potentially worsened inflammation in colitis models. In addition, metabolomic profiling revealed alterations in colonic metabolites involved in key Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, including NF-kappa B signaling, Th1 and Th2 cell differentiation.DiscussionThese findings reveal that the mouse chymase MCPT-4 plays important roles in maintaining the intestinal homeostasis during colitis, potentially through regulation of colonic cytokines, microbial and metabolic networks.https://www.frontiersin.org/articles/10.3389/fcimb.2025.1481927/fullulcerative colitismicrobiotachymaseexacerbationmetabolism |
| spellingShingle | Zhiqiang Li Zhiqiang Li Zhiqiang Li Xiaoyuan Kuang Dashuang Mo Magnus Åbrink Ge Shan Jin-ping Li Can Yang Yuexi Wang Tao Shen Weiwei Yu The deficiency of chymase mast cell protease 4 exacerbates dextran sulfate sodium salt-induced colitis in mice and is associated with altered microbiota and metabolome profiles Frontiers in Cellular and Infection Microbiology ulcerative colitis microbiota chymase exacerbation metabolism |
| title | The deficiency of chymase mast cell protease 4 exacerbates dextran sulfate sodium salt-induced colitis in mice and is associated with altered microbiota and metabolome profiles |
| title_full | The deficiency of chymase mast cell protease 4 exacerbates dextran sulfate sodium salt-induced colitis in mice and is associated with altered microbiota and metabolome profiles |
| title_fullStr | The deficiency of chymase mast cell protease 4 exacerbates dextran sulfate sodium salt-induced colitis in mice and is associated with altered microbiota and metabolome profiles |
| title_full_unstemmed | The deficiency of chymase mast cell protease 4 exacerbates dextran sulfate sodium salt-induced colitis in mice and is associated with altered microbiota and metabolome profiles |
| title_short | The deficiency of chymase mast cell protease 4 exacerbates dextran sulfate sodium salt-induced colitis in mice and is associated with altered microbiota and metabolome profiles |
| title_sort | deficiency of chymase mast cell protease 4 exacerbates dextran sulfate sodium salt induced colitis in mice and is associated with altered microbiota and metabolome profiles |
| topic | ulcerative colitis microbiota chymase exacerbation metabolism |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2025.1481927/full |
| work_keys_str_mv | AT zhiqiangli thedeficiencyofchymasemastcellprotease4exacerbatesdextransulfatesodiumsaltinducedcolitisinmiceandisassociatedwithalteredmicrobiotaandmetabolomeprofiles AT zhiqiangli thedeficiencyofchymasemastcellprotease4exacerbatesdextransulfatesodiumsaltinducedcolitisinmiceandisassociatedwithalteredmicrobiotaandmetabolomeprofiles AT zhiqiangli thedeficiencyofchymasemastcellprotease4exacerbatesdextransulfatesodiumsaltinducedcolitisinmiceandisassociatedwithalteredmicrobiotaandmetabolomeprofiles AT xiaoyuankuang thedeficiencyofchymasemastcellprotease4exacerbatesdextransulfatesodiumsaltinducedcolitisinmiceandisassociatedwithalteredmicrobiotaandmetabolomeprofiles AT dashuangmo thedeficiencyofchymasemastcellprotease4exacerbatesdextransulfatesodiumsaltinducedcolitisinmiceandisassociatedwithalteredmicrobiotaandmetabolomeprofiles AT magnusabrink thedeficiencyofchymasemastcellprotease4exacerbatesdextransulfatesodiumsaltinducedcolitisinmiceandisassociatedwithalteredmicrobiotaandmetabolomeprofiles AT geshan thedeficiencyofchymasemastcellprotease4exacerbatesdextransulfatesodiumsaltinducedcolitisinmiceandisassociatedwithalteredmicrobiotaandmetabolomeprofiles AT jinpingli thedeficiencyofchymasemastcellprotease4exacerbatesdextransulfatesodiumsaltinducedcolitisinmiceandisassociatedwithalteredmicrobiotaandmetabolomeprofiles AT canyang thedeficiencyofchymasemastcellprotease4exacerbatesdextransulfatesodiumsaltinducedcolitisinmiceandisassociatedwithalteredmicrobiotaandmetabolomeprofiles AT yuexiwang thedeficiencyofchymasemastcellprotease4exacerbatesdextransulfatesodiumsaltinducedcolitisinmiceandisassociatedwithalteredmicrobiotaandmetabolomeprofiles AT taoshen thedeficiencyofchymasemastcellprotease4exacerbatesdextransulfatesodiumsaltinducedcolitisinmiceandisassociatedwithalteredmicrobiotaandmetabolomeprofiles AT weiweiyu thedeficiencyofchymasemastcellprotease4exacerbatesdextransulfatesodiumsaltinducedcolitisinmiceandisassociatedwithalteredmicrobiotaandmetabolomeprofiles AT zhiqiangli deficiencyofchymasemastcellprotease4exacerbatesdextransulfatesodiumsaltinducedcolitisinmiceandisassociatedwithalteredmicrobiotaandmetabolomeprofiles AT zhiqiangli deficiencyofchymasemastcellprotease4exacerbatesdextransulfatesodiumsaltinducedcolitisinmiceandisassociatedwithalteredmicrobiotaandmetabolomeprofiles AT zhiqiangli deficiencyofchymasemastcellprotease4exacerbatesdextransulfatesodiumsaltinducedcolitisinmiceandisassociatedwithalteredmicrobiotaandmetabolomeprofiles AT xiaoyuankuang deficiencyofchymasemastcellprotease4exacerbatesdextransulfatesodiumsaltinducedcolitisinmiceandisassociatedwithalteredmicrobiotaandmetabolomeprofiles AT dashuangmo deficiencyofchymasemastcellprotease4exacerbatesdextransulfatesodiumsaltinducedcolitisinmiceandisassociatedwithalteredmicrobiotaandmetabolomeprofiles AT magnusabrink deficiencyofchymasemastcellprotease4exacerbatesdextransulfatesodiumsaltinducedcolitisinmiceandisassociatedwithalteredmicrobiotaandmetabolomeprofiles AT geshan deficiencyofchymasemastcellprotease4exacerbatesdextransulfatesodiumsaltinducedcolitisinmiceandisassociatedwithalteredmicrobiotaandmetabolomeprofiles AT jinpingli deficiencyofchymasemastcellprotease4exacerbatesdextransulfatesodiumsaltinducedcolitisinmiceandisassociatedwithalteredmicrobiotaandmetabolomeprofiles AT canyang deficiencyofchymasemastcellprotease4exacerbatesdextransulfatesodiumsaltinducedcolitisinmiceandisassociatedwithalteredmicrobiotaandmetabolomeprofiles AT yuexiwang deficiencyofchymasemastcellprotease4exacerbatesdextransulfatesodiumsaltinducedcolitisinmiceandisassociatedwithalteredmicrobiotaandmetabolomeprofiles AT taoshen deficiencyofchymasemastcellprotease4exacerbatesdextransulfatesodiumsaltinducedcolitisinmiceandisassociatedwithalteredmicrobiotaandmetabolomeprofiles AT weiweiyu deficiencyofchymasemastcellprotease4exacerbatesdextransulfatesodiumsaltinducedcolitisinmiceandisassociatedwithalteredmicrobiotaandmetabolomeprofiles |