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Sphk1 promotes ulcerative colitis via activating JAK2/STAT3 signaling pathway

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Abstract

Ulcerative colitis (UC) is a chronic non-specific inflammatory disease of the colon and rectum. The cause of ulcerative colitis is still unclear, although there may be a hereditary factor. SphK1 has been reported to exhibit an inhibitory effect on the occurrence and development of inflammation; however, the association between SphK1 and the progression of UC remains unclear. The aim of the present study was to investigate the effect of Sphk1 on the progression of UC. The proliferation of RAW264.7 cells was determined using a Cell Counting Kit-8 assay and apoptosis was measured using flow cytometry. The levels of pro-inflammatory cytokines secreted by RAW264.7 cells were investigated using ELISA kits and the protein expression levels in RAW264.7 cells were examined by western blotting. A dextran sulfate sodium (DSS)-induced mouse model was established to investigate the effect of SphK1 on the progression of UC in vivo. Overexpression of Sphk1 significantly increased the proliferation and inhibited the apoptosis of RAW264.7 cells. Additionally, overexpression of Sphk1 increased the secretion of pro-inflammatory cytokines and activated the JAK2/STAT3 signaling pathway in RAW264.7 cells, and JSI-124 partially suppressed these effects. Furthermore, SphK1-small interfering RNA or JSI-124 partially rescued lipopolysaccharide-induced proliferation and pro-inflammatory effects on RAW264.7 cells. The SphK1 inhibitor (PF-543) had an inhibitory effect on DSS-induced UC mice. Sphk1 had significant pro-inflammatory effects on the progression of UC, and may thus be a potential novel therapeutic target for the treatment of UC.

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Acknowledgements

This research was supported by the Youth Fund of Beijing TsingHua Changgung Hospital (12016C1007).

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  1. Department of Gastroenterology, Beijing TsingHua Changgung Hospital, No. 168, LiTang Road, Beijing, 102218, China

    Jiawen Liu & Bo Jiang

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  1. Jiawen Liu
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  2. Bo Jiang
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Correspondence to Bo Jiang.

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All experimental procedures were approved by the Ethical Committee of Beijing TsingHua Changgung Hospital, and the National Institutes of Health guide for the care and use of laboratory animals was followed.

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Liu, J., Jiang, B. Sphk1 promotes ulcerative colitis via activating JAK2/STAT3 signaling pathway. Human Cell 33, 57–66 (2020). https://doi.org/10.1007/s13577-019-00283-z

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