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...

Full description

Saved in:
Bibliographic Details
Main Authors: 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
Format: Article
Language:English
Published: Wiley 2025-01-01
Series:Food Frontiers
Subjects:
Online Access:https://doi.org/10.1002/fft2.516
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849328221373333504
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
work_keys_str_mv AT zetianwang hucmscsregulatebileacidmetabolismtopreventheartfailureinducedintestinalinjurybyinhibitingtheactivationofthestat3nfkbmapksignalingpathwayviatgr5
AT weiluo hucmscsregulatebileacidmetabolismtopreventheartfailureinducedintestinalinjurybyinhibitingtheactivationofthestat3nfkbmapksignalingpathwayviatgr5
AT qingwang hucmscsregulatebileacidmetabolismtopreventheartfailureinducedintestinalinjurybyinhibitingtheactivationofthestat3nfkbmapksignalingpathwayviatgr5
AT chunzhengliu hucmscsregulatebileacidmetabolismtopreventheartfailureinducedintestinalinjurybyinhibitingtheactivationofthestat3nfkbmapksignalingpathwayviatgr5
AT yanshangong hucmscsregulatebileacidmetabolismtopreventheartfailureinducedintestinalinjurybyinhibitingtheactivationofthestat3nfkbmapksignalingpathwayviatgr5
AT baitianli hucmscsregulatebileacidmetabolismtopreventheartfailureinducedintestinalinjurybyinhibitingtheactivationofthestat3nfkbmapksignalingpathwayviatgr5
AT xuejiaozeng hucmscsregulatebileacidmetabolismtopreventheartfailureinducedintestinalinjurybyinhibitingtheactivationofthestat3nfkbmapksignalingpathwayviatgr5
AT jiaqilin hucmscsregulatebileacidmetabolismtopreventheartfailureinducedintestinalinjurybyinhibitingtheactivationofthestat3nfkbmapksignalingpathwayviatgr5
AT zehuasu hucmscsregulatebileacidmetabolismtopreventheartfailureinducedintestinalinjurybyinhibitingtheactivationofthestat3nfkbmapksignalingpathwayviatgr5
AT xinli hucmscsregulatebileacidmetabolismtopreventheartfailureinducedintestinalinjurybyinhibitingtheactivationofthestat3nfkbmapksignalingpathwayviatgr5
AT yongzeyu hucmscsregulatebileacidmetabolismtopreventheartfailureinducedintestinalinjurybyinhibitingtheactivationofthestat3nfkbmapksignalingpathwayviatgr5
AT zhongminliu hucmscsregulatebileacidmetabolismtopreventheartfailureinducedintestinalinjurybyinhibitingtheactivationofthestat3nfkbmapksignalingpathwayviatgr5
AT linggao hucmscsregulatebileacidmetabolismtopreventheartfailureinducedintestinalinjurybyinhibitingtheactivationofthestat3nfkbmapksignalingpathwayviatgr5
AT lijunliao hucmscsregulatebileacidmetabolismtopreventheartfailureinducedintestinalinjurybyinhibitingtheactivationofthestat3nfkbmapksignalingpathwayviatgr5