FGF1ΔHBS ameliorates DSS‐induced ulcerative colitis by reducing neutrophil recruitment through the MAPK pathway

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Auteurs principaux: Shuang Feng, Yanyan Jin, Xinrui Ni, Haoxin Zheng, Linling Wu, Ying Xia, Changzhi Zhou, Tong Liang, Yunfei Zhu, Juyi Xu, Qijin Wu, Yong Yang, Longwei Zhao, Shentian Zhuang, Xianjing Li
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author Shuang Feng
Yanyan Jin
Xinrui Ni
Haoxin Zheng
Linling Wu
Ying Xia
Changzhi Zhou
Tong Liang
Yunfei Zhu
Juyi Xu
Qijin Wu
Yong Yang
Longwei Zhao
Shentian Zhuang
Xianjing Li
author_facet Shuang Feng
Yanyan Jin
Xinrui Ni
Haoxin Zheng
Linling Wu
Ying Xia
Changzhi Zhou
Tong Liang
Yunfei Zhu
Juyi Xu
Qijin Wu
Yong Yang
Longwei Zhao
Shentian Zhuang
Xianjing Li
Shuang Feng
Yanyan Jin
Xinrui Ni
Haoxin Zheng
Linling Wu
Ying Xia
Changzhi Zhou
Tong Liang
Yunfei Zhu
Juyi Xu
Qijin Wu
Yong Yang
Longwei Zhao
Shentian Zhuang
Xianjing Li
collection Wiley Open Access
contents FGF1ΔHBS ameliorates DSS‐induced ulcerative colitis by reducing neutrophil recruitment through the MAPK pathway Shuang Feng Yanyan Jin Xinrui Ni Haoxin Zheng Linling Wu Ying Xia Changzhi Zhou Tong Liang Yunfei Zhu Juyi Xu Qijin Wu Yong Yang Longwei Zhao Shentian Zhuang Xianjing Li British Journal of Pharmacology Background and PurposeInflammatory bowel diseases (IBDs) constitute chronic inflammatory disease of the gastrointestinal tract, with escalating global prevalence. There is a pressing demand for safe and effective treatments for IBDs. Fibroblast growth factor 1 (FGF1) variant FGF1ΔHBS, characterised by reduced mitogenic capacity, has shown promising therapeutic potential in various inflammatory conditions, including obesity and diabetic nephropathy. Hence, exploring the therapeutic impact of FGF1ΔHBS on colitis is warranted.Experimental ApproachThe protective role of FGF1ΔHBS was evaluated using a dextran sulphate sodium (DSS)‐induced colitis model in mice. RNA‐seq analysis was performed on colonic tissues. Inflammatory factor expression was examined by quantitative real‐time polymerase chain reaction (PCR) and enzyme‐linked immunosorbent assay. Flow cytometry and immunofluorescence staining were employed to confirm the inhibitory effect of FGF1ΔHBS on neutrophil recruitment. Western blotting was performed to explore the mitogen‐activated protein kinase (MAPK) signalling pathway.Key ResultsFGF1ΔHBS significantly alleviated DSS‐induced colitis, as indicated by reduced Disease Activity Index scores and less histological injury to the colon. Additionally, FGF1ΔHBS decreased the expression of pro‐inflammatory factors. Mechanistically, FGF1ΔHBS inhibited neutrophil‐associated chemokine expression in intestinal epithelial cells by suppressing the MAPK signalling pathway, thereby reducing neutrophil recruitment and attenuating neutrophil‐mediated intestinal inflammation.Conclusion and ImplicationsFGF1ΔHBS protects against DSS‐induced colitis in mice by inhibiting neutrophil recruitment through MAPK activity suppression, suggesting a potential therapeutic strategy for preventing IBDs.LINKED ARTICLESThis article is part of a themed issue Drugs and Drug Targets in Metabolic and Chronic Inflammatory Diseases. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v182.20/issuetoc 10.1111/bph.70049 http://onlinelibrary.wiley.com/termsAndConditions#vor
doi_str_mv 10.1111/bph.70049
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institution Wiley Open Access
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publishDate 2025
publisher Wiley
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spellingShingle FGF1ΔHBS ameliorates DSS‐induced ulcerative colitis by reducing neutrophil recruitment through the MAPK pathway
Shuang Feng
Yanyan Jin
Xinrui Ni
Haoxin Zheng
Linling Wu
Ying Xia
Changzhi Zhou
Tong Liang
Yunfei Zhu
Juyi Xu
Qijin Wu
Yong Yang
Longwei Zhao
Shentian Zhuang
Xianjing Li
British Journal of Pharmacology
FGF1ΔHBS ameliorates DSS‐induced ulcerative colitis by reducing neutrophil recruitment through the MAPK pathway Shuang Feng Yanyan Jin Xinrui Ni Haoxin Zheng Linling Wu Ying Xia Changzhi Zhou Tong Liang Yunfei Zhu Juyi Xu Qijin Wu Yong Yang Longwei Zhao Shentian Zhuang Xianjing Li British Journal of Pharmacology Background and PurposeInflammatory bowel diseases (IBDs) constitute chronic inflammatory disease of the gastrointestinal tract, with escalating global prevalence. There is a pressing demand for safe and effective treatments for IBDs. Fibroblast growth factor 1 (FGF1) variant FGF1ΔHBS, characterised by reduced mitogenic capacity, has shown promising therapeutic potential in various inflammatory conditions, including obesity and diabetic nephropathy. Hence, exploring the therapeutic impact of FGF1ΔHBS on colitis is warranted.Experimental ApproachThe protective role of FGF1ΔHBS was evaluated using a dextran sulphate sodium (DSS)‐induced colitis model in mice. RNA‐seq analysis was performed on colonic tissues. Inflammatory factor expression was examined by quantitative real‐time polymerase chain reaction (PCR) and enzyme‐linked immunosorbent assay. Flow cytometry and immunofluorescence staining were employed to confirm the inhibitory effect of FGF1ΔHBS on neutrophil recruitment. Western blotting was performed to explore the mitogen‐activated protein kinase (MAPK) signalling pathway.Key ResultsFGF1ΔHBS significantly alleviated DSS‐induced colitis, as indicated by reduced Disease Activity Index scores and less histological injury to the colon. Additionally, FGF1ΔHBS decreased the expression of pro‐inflammatory factors. Mechanistically, FGF1ΔHBS inhibited neutrophil‐associated chemokine expression in intestinal epithelial cells by suppressing the MAPK signalling pathway, thereby reducing neutrophil recruitment and attenuating neutrophil‐mediated intestinal inflammation.Conclusion and ImplicationsFGF1ΔHBS protects against DSS‐induced colitis in mice by inhibiting neutrophil recruitment through MAPK activity suppression, suggesting a potential therapeutic strategy for preventing IBDs.LINKED ARTICLESThis article is part of a themed issue Drugs and Drug Targets in Metabolic and Chronic Inflammatory Diseases. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v182.20/issuetoc 10.1111/bph.70049 http://onlinelibrary.wiley.com/termsAndConditions#vor
title FGF1ΔHBS ameliorates DSS‐induced ulcerative colitis by reducing neutrophil recruitment through the MAPK pathway
topic British Journal of Pharmacology
url https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bph.70049