Silencing MARK4 inhibits apoptosis and inflammatory factor expression of in ulcerative colitis via NF-κB signaling pathway
10.13431/j.cnki.immunol.j.20240018
- VernacularTitle:沉默MARK4通过NF-κB信号通路抑制溃疡性结肠炎细胞焦亡和炎症因子表达
- Author:
Lu YE
1
;
Shengtao LIAO
;
Chuanfei LI
;
Jianlin SU
;
Xinglian YU
;
Yanhui WANG
;
Ya SONG
;
Lin LYU
Author Information
1. 400010,重庆医科大学附属第二医院消化内科
- Keywords:
Ulcerative colitis;
MARK4;
Apoptosis;
Inflammation;
NF-κB signaling Pathway
- From:
Immunological Journal
2024;40(2):131-137
- CountryChina
- Language:Chinese
-
Abstract:
This study was designed to investigate the effect of silencing microtubule-affinity regulating kinase 4(MARK4)on the apoptosis,inflammatory cytokine release and intestinal barrier protein expression of FHC cells in a lipopolysaccharide(LPS)-induced ulcerative colitis(UC)model,and the underlying molecular mechanisms.Western blot analysis was used to measure the expression levels of MARK4 and apoptosis-related factors including Caspase-1,NLRP3,and GSDMD in colon tissues from both UC patients and healthy individuals,as well as in LPS-induced FHC cell inflammation model.FHC cells was transfected with shRNA to silence MARK4.In control(normal FHC cells),LPS(LPS-stimulated FHC cells),and MARK4-silenced+LPS(shRNA-and LPS-treated FHC cells)groups,the expression levels of Caspase-1,NLRP3,GSDMD,intestinal barrier proteins,and NF-κB pathway-related proteins were assessed by Western blotting.ELISA and RT-qPCR were used to measure the expression levels of inflammatory cytokines IL-1β,IL-6,and TNF-α;flow cytometry was utilized to assess apoptosis.Data showed that both in UC patient colon tissues and the in vitro LPS-induced FHC cell UC inflammation model,there was a significant increase in the expression of MARK4 and apoptosis-related proteins including NLRP3,Caspase-1,and GSDMD.Silencing MARK4 inhibited the expression of these apoptosis-related proteins and downregulated the inflammatory cytokines IL-1β,IL-6,and TNF-α in LPS-induced FHC cells.Silencing MARK4 also reduced apoptosis,increased the expression of intestinal barrier proteins ZO-1,Occludin,and upregulated Claudin2.Gene Set Enrichment Analysis(GSEA)indicated a positive correlation between MARK4 and the NF-κB signaling pathway.Furthermore,silencing of MARK4 inhibited the expression levels of p-P65 and p-IKKα in the NF-κB pathway.In conclusion,MARK4 is significantly upregulated in UC tissues and cells.Silencing MARK4 inhibits the activation of the NF-κB signaling pathway,thereby inhibiting the apoptosis and inflammatory factor expression of UC cells.Thus,MARK4 could be a potential therapeutic target for UC patients.
