Inhibition of visfatin alleviates sepsis-induced intestinal damage by inhibiting Hippo signaling pathway View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2022-06-22

AUTHORS

Zhong-Shen Kuang, Yu-Xin Leng, Ning Yang, Zheng-Qian Li, Ya-Nan Zong, Deng-Yang Han, Yue Li, Jin-Dan He, Xing-Ning Mi, Zhu-Kai Cong, Xi Zhu, Chang-Yi Wu, Xiang-Yang Guo

ABSTRACT

BackgroundThe aim of this study is to investigate role of Visfatin, one of the pro-inflammatory adipokines, in sepsis-induced intestinal injury and to clarify the potential mechanism.MethodsC57BL/6 mice underwent cecal ligation and puncture (CLP) surgery to establish sepsis model in vivo. Intestinal epithelial cells were stimulated with LPS to mimic sepsis-induced intestinal injury in vitro. FK866 (the inhibitor of Visfatin) with or without XMU-MP-1 (the inhibitor of Hippo signaling) was applied for treatment. The expression levels of Visfatin, NF-κB and Hippo signaling pathways-related proteins were detected by western blot or immunohistochemistry. The intestinal cell apoptosis and intestinal injury were investigated by TUNEL staining and H&E staining, respectively. ELISA was used to determine the production of inflammatory cytokines.ResultsThe expression of Visfatin increased in CLP mice. FK866 reduced intestinal pathological injury, inflammatory cytokines production, and intestinal cell apoptosis in sepsis mice. Meanwhile, FK866 affected NF-κB and Hippo signaling pathways. Additionally, the effects of FK866 on inflammatory response, apoptosis, Hippo signaling and NF-κB signaling were partly abolished by XMU-MP-1, the inhibitor of Hippo signaling. In vitro experiments also revealed that FK866 exhibited a protective role against LPS-induced inflammatory response and apoptosis in intestinal cells, as well as regulating NF-κB and Hippo signaling, whereas addition of XMU-MP-1 weakened the protective effects of FK866.ConclusionIn short, this study demonstrated that inhibition of Visfatin might alleviate sepsis-induced intestinal injury through Hippo signaling pathway, supporting a further research on Visfatin as a therapeutic target. More... »

PAGES

911-922

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00011-022-01593-z

DOI

http://dx.doi.org/10.1007/s00011-022-01593-z

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1148869541

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/35731253


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65 inhibition
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81 pathway
82 pathway-related proteins
83 potential mechanisms
84 pro-inflammatory adipokines
85 production
86 protective effect
87 protective role
88 protein
89 puncture surgery
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92 role
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94 sepsis mice
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105 vivo
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