hUCMSCs Regulate Bile Acid Metabolism to Prevent Heart Failure–Induced Intestinal Injury by Inhibiting the Activation of the STAT3/NF‐κB/MAPK Signaling Pathway via TGR5
ABSTRACT The protective effects of human umbilical cord mesenchymal stem cells (hUCMSCs) on heart failure (HF)‐induced intestinal injury have not been fully understood. Flow cytometry and immunofluorescence analysis revealed that hUCMSCs renewed themselves, grew, and transformed into various cell ty...
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| Format: | Article |
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Wiley
2025-01-01
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| Series: | Food Frontiers |
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| Online Access: | https://doi.org/10.1002/fft2.516 |
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| author | Zetian Wang Wei Luo Qing Wang Chunzheng Liu Yanshan Gong Baitian Li Xuejiao Zeng Jiaqi Lin Zehua Su Xin Li Yongze Yu Zhongmin Liu Ling Gao Lijun Liao |
| author_facet | Zetian Wang Wei Luo Qing Wang Chunzheng Liu Yanshan Gong Baitian Li Xuejiao Zeng Jiaqi Lin Zehua Su Xin Li Yongze Yu Zhongmin Liu Ling Gao Lijun Liao |
| author_sort | Zetian Wang |
| collection | DOAJ |
| description | ABSTRACT The protective effects of human umbilical cord mesenchymal stem cells (hUCMSCs) on heart failure (HF)‐induced intestinal injury have not been fully understood. Flow cytometry and immunofluorescence analysis revealed that hUCMSCs renewed themselves, grew, and transformed into various cell types. Meanwhile, hUCMSCs safeguarded against intestinal damage, regulated imbalances in the intestinal flora and bile acid metabolism, and enhanced the levels of hyodeoxycholic acid (HDCA) in pigs with HF. HDCA protected against HF‐induced intestinal injury in mice through Takeda G protein–coupled receptor 5 (TGR5). Protein analysis showed that HDCA exerted protective effects on the intestines via the signal transducer and activator of transcription 3 (STAT3)/nuclear factor kappa B (NF‐κB)/mitogen‐activated protein kinase (MAPK) signaling pathway. Mouse experiments revealed that HDCA bound to TGR5 to inhibit MAPK and NF‐κB signaling pathway activation, which relies on the STAT3 signaling pathway. Moreover, hUCMSCs protected against intestinal injury in the pig model of HF by suppressing the activation of the STAT3/NF‐κB/MAPK signaling pathway via TGR5. |
| format | Article |
| id | doaj-art-4d0e0865d414465692c1811161fac8a2 |
| institution | Kabale University |
| issn | 2643-8429 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Food Frontiers |
| spelling | doaj-art-4d0e0865d414465692c1811161fac8a22025-08-20T03:47:40ZengWileyFood Frontiers2643-84292025-01-016157558910.1002/fft2.516hUCMSCs Regulate Bile Acid Metabolism to Prevent Heart Failure–Induced Intestinal Injury by Inhibiting the Activation of the STAT3/NF‐κB/MAPK Signaling Pathway via TGR5Zetian Wang0Wei Luo1Qing Wang2Chunzheng Liu3Yanshan Gong4Baitian Li5Xuejiao Zeng6Jiaqi Lin7Zehua Su8Xin Li9Yongze Yu10Zhongmin Liu11Ling Gao12Lijun Liao13Department of Anesthesiology and Pain Management, Shanghai East Hospital Tongji University School of Medicine Shanghai ChinaDepartment of Neurosurgery, Shanghai East Hospital, School of Medicine Tongji University Shanghai ChinaDepartment of Anesthesiology and Pain Management, Shanghai East Hospital Tongji University School of Medicine Shanghai ChinaDepartment of Anesthesiology and Pain Management, Shanghai East Hospital Tongji University School of Medicine Shanghai ChinaTranslational Medical Center for Stem Cell Therapy & Institutes for Regenerative Medicine, Shanghai East Hospital Tongji University School of Medicine Shanghai ChinaDepartment of Anesthesiology and Pain Management, Shanghai East Hospital Tongji University School of Medicine Shanghai ChinaDepartment of Anesthesiology and Pain Management, Shanghai East Hospital Tongji University School of Medicine Shanghai ChinaDepartment of Anesthesiology and Pain Management, Shanghai East Hospital Tongji University School of Medicine Shanghai ChinaDepartment of Anesthesiology and Pain Management, Shanghai East Hospital Tongji University School of Medicine Shanghai ChinaDepartment of Anesthesiology and Pain Management, Shanghai East Hospital Tongji University School of Medicine Shanghai ChinaDepartment of Anesthesiology and Pain Management, Shanghai East Hospital Tongji University School of Medicine Shanghai ChinaDepartment of Anesthesiology and Pain Management, Shanghai East Hospital Tongji University School of Medicine Shanghai ChinaTranslational Medical Center for Stem Cell Therapy & Institutes for Regenerative Medicine, Shanghai East Hospital Tongji University School of Medicine Shanghai ChinaDepartment of Anesthesiology and Pain Management, Shanghai East Hospital Tongji University School of Medicine Shanghai ChinaABSTRACT The protective effects of human umbilical cord mesenchymal stem cells (hUCMSCs) on heart failure (HF)‐induced intestinal injury have not been fully understood. Flow cytometry and immunofluorescence analysis revealed that hUCMSCs renewed themselves, grew, and transformed into various cell types. Meanwhile, hUCMSCs safeguarded against intestinal damage, regulated imbalances in the intestinal flora and bile acid metabolism, and enhanced the levels of hyodeoxycholic acid (HDCA) in pigs with HF. HDCA protected against HF‐induced intestinal injury in mice through Takeda G protein–coupled receptor 5 (TGR5). Protein analysis showed that HDCA exerted protective effects on the intestines via the signal transducer and activator of transcription 3 (STAT3)/nuclear factor kappa B (NF‐κB)/mitogen‐activated protein kinase (MAPK) signaling pathway. Mouse experiments revealed that HDCA bound to TGR5 to inhibit MAPK and NF‐κB signaling pathway activation, which relies on the STAT3 signaling pathway. Moreover, hUCMSCs protected against intestinal injury in the pig model of HF by suppressing the activation of the STAT3/NF‐κB/MAPK signaling pathway via TGR5.https://doi.org/10.1002/fft2.516HDCAheart failurehUCMSCsintestinal injuryTGR5 |
| spellingShingle | Zetian Wang Wei Luo Qing Wang Chunzheng Liu Yanshan Gong Baitian Li Xuejiao Zeng Jiaqi Lin Zehua Su Xin Li Yongze Yu Zhongmin Liu Ling Gao Lijun Liao hUCMSCs Regulate Bile Acid Metabolism to Prevent Heart Failure–Induced Intestinal Injury by Inhibiting the Activation of the STAT3/NF‐κB/MAPK Signaling Pathway via TGR5 Food Frontiers HDCA heart failure hUCMSCs intestinal injury TGR5 |
| title | hUCMSCs Regulate Bile Acid Metabolism to Prevent Heart Failure–Induced Intestinal Injury by Inhibiting the Activation of the STAT3/NF‐κB/MAPK Signaling Pathway via TGR5 |
| title_full | hUCMSCs Regulate Bile Acid Metabolism to Prevent Heart Failure–Induced Intestinal Injury by Inhibiting the Activation of the STAT3/NF‐κB/MAPK Signaling Pathway via TGR5 |
| title_fullStr | hUCMSCs Regulate Bile Acid Metabolism to Prevent Heart Failure–Induced Intestinal Injury by Inhibiting the Activation of the STAT3/NF‐κB/MAPK Signaling Pathway via TGR5 |
| title_full_unstemmed | hUCMSCs Regulate Bile Acid Metabolism to Prevent Heart Failure–Induced Intestinal Injury by Inhibiting the Activation of the STAT3/NF‐κB/MAPK Signaling Pathway via TGR5 |
| title_short | hUCMSCs Regulate Bile Acid Metabolism to Prevent Heart Failure–Induced Intestinal Injury by Inhibiting the Activation of the STAT3/NF‐κB/MAPK Signaling Pathway via TGR5 |
| title_sort | hucmscs regulate bile acid metabolism to prevent heart failure induced intestinal injury by inhibiting the activation of the stat3 nf κb mapk signaling pathway via tgr5 |
| topic | HDCA heart failure hUCMSCs intestinal injury TGR5 |
| url | https://doi.org/10.1002/fft2.516 |
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