FOSL1 knockdown ameliorates DSS-induced inflammation and barrier damage in ulcerative colitis via MMP13 downregulation.

Ulcerative colitis (UC) is a chronic inflammatory disease of the colon. Fos-related antigen 1 is highly expressed in mild UC and affects the maintenance and delayed recurrence of inflammatory bowel disease. Therefore the present study aimed to investigate the role of Fos-like antigen-1 (FOSL1) in UC. Use of the JASPAR database predicted the possible interaction of FOSL1 and the MMP13 promoter. FOSL1 and MMP13 mRNA and protein expression levels in dextran sodium sulfate (DSS)-induced HT29 cells and colon tissues of a UC mice model were determined using reverse transcription-quantitative PCR and western blotting, respectively. MMP13 promoter activity was determined using the dual-luciferase reporter assay, the relationship between FOSL1 and MMP13 promoter was determined using chromatin immunoprecipitation, inflammatory factor levels were quantified using ELISA, cell monolayer permeability analysis was performed using transepithelial electrical resistance measurements and tight junction protein expression levels were determined by western blotting. After constructing a UC mice model, mice colonic injury was determined with the quantification of colon length, H&E staining and disease activity index. The results demonstrated that FOSL1 and MMP13 were upregulated in DSS-induced HT29 cells and tissues. FOSL1 was also determined to be bound to the MMP13 promoter region and was demonstrated to upregulate MMP13 expression levels. Furthermore, FOSL1 knockdown inhibited DSS-induced inflammation and barrier damage in HT29 cells via MMP13 downregulation. FOSL1 knockdown also ameliorated colonic injury, inflammation and barrier damage in the tissues of the UC mice model via MMP13 downregulation. Overall, FOSL1 knockdown was demonstrated to potentially ameliorate DSS-induced inflammatory injury and protect the intestinal barrier integrity in the UC mice model via MMP13 downregulation.

Omentin-1 attenuates inflammation and barrier damage in DSS-induced ulcerative colitis in mice by inhibiting endoplasmic reticulum stress.

Ulcerative colitis (UC) is a diffuse inflammatory disease that occurs in the mucosa of the colon and rectum. Research illustrated that omentin-1 level was significantly lower in the serum of patients with UC. This study systematically examines the emerging roles of omentin-1 in UC and its related mechanisms. Omentin-1 level in dextran sulfate sodium (DSS)-induced mice was examined by Western blot and RT-PCR. The expressions of endoplasmic reticulum (ER) stress-related proteins were detected adopting Western blot with or without the addition of ER stress inducer tunicamycin (TM) in colitis mice. Subsequently, in DSS-induced UC mice, colonic damage was determined by HE staining, body weight, colon length, and disease activity index (DAI). Inflammation and barrier damage were examined by ELISA and Western blot. Cell apoptosis in colon tissues was examined by TUNEL and Western blot. Omentin-1 expressed lowly in DSS-induced colon tissues of UC mice, and its overexpression inhibited ER stress. Additionally, overexpression of omentin-1 also inhibited DSS-induced colon damage, inflammation, barrier damage and cell apoptosis in UC mice; however, these changes were partly abolished by TM administration. In conclusion, omentin-1 attenuates DSS-induced inflammation and barrier damage in UC mice by inhibiting ER stress, suggesting omentin-1 may be a useful target for the treatment of UC.

Transcription factor paired related homeobox 1 (PRRX1) activates matrix metalloproteinases (MMP)13, which promotes the dextran sulfate sodium-induced inflammation and barrier dysfunction of NCM460 cells.

Paired related homeobox 1 (PRRX1) is a newly identified transcription factor that regulates the expression of various genes. We aimed to investigate the roles of PRRX1 and Matrix metalloproteinases (MMP)13 in dextran sulfate sodium (DSS)-induced inflammation and barrier dysfunction of NCM460 cells. PRRX1 expression in the mucosal tissues of patients with ulcerative colitis was analyzed using the GSE87466 microarray. PRRX1 and MMP13 expression was examined using Western blotting and RT-qPCR following the exposure of the NCM460 cells to DSS. The JASPAR database was used to predict the binding sites of PRRX1 to the MMP13 promoter, which was verified by luciferase reporter and chromatin immunoprecipitation assays. MMP13 expression was then detected following PRRX1 silencing or overexpression. The levels of inflammatory factors were determined using ELISA. Finally, the expression of intestinal barrier function-related proteins was evaluated using Western blotting and cellular permeability was detected by Transepithelial electrical resistance. PRRX1 was upregulated in the mucosal tissue samples of patients with UC. DSS induction upregulated PRRX1 and MMP13 expression. PRRX1 bound to the promoter of MMP13, which was further supported by the decreased expression of MMP13 observed following PRRX1 knockdown and its increased expression following PRRX1 overexpression. Furthermore, PRRX1 deletion decreased TNF-α, IL-1ß and IL-6 levels in the DSS-challenged NCM460 cells, which were subjected to MMP13 overexpression. Moreover, PRRX1 silencing upregulated ZO-1, occludin and claudin-1 expression and elevated the TEER value, whereas MMP13 overexpression attenuated these effects. Collectively, PRRX1 activates MMP13, which in turn promotes the DSS-induced inflammation and barrier dysfunction of NCM460 cells.

Nonsurgical Secondary Prophylaxis of Esophageal Variceal Bleeding in Cirrhotic Patients: A Systematic Review and Network Meta-analysis.

INTRODUCTION: The aim of this study was to evaluate the effectiveness of nonsurgical secondary prophylaxis interventions for esophageal varices (EV) rebleeding in cirrhotic patients using network meta-analysis. MATERIALS AND METHODS: Secondary prophylaxis of EV rebleeding in cirrhosis is searched on PubMed, Embase, and the Cochrane Library databases. The quality of literatures was extracted by 2 independent investigators according to the requirements of Cochrane Handbook for Systematic Reviews of Interventions, Version 5.0.0. Meta-analysis was performed on Review Manager 5.3 software for the incidence of cirrhosis EV rebleeding, rebleeding-related mortality, and overall mortality; and STATA 15.1 software was used for network meta-analysis. RESULTS: In all, 57 randomized controlled trials were reviewed. Endoscopic band ligation (EBL)+argon plasma coagulation has not been recommended by guidelines, and it is rarely used; the number of existing studies and the sample size are small. Considering poor stability of the combined results, these studies were excluded; 55 literatures were included. In terms of reducing the incidence of rebleeding, transjugular intrahepatic portosystemic shunt (TIPS) surface under the cumulative ranking curve (SUCRA) (94.3%) was superior to EBL+endoscopic injection sclerotherapy (EIS) (84.4%), EIS+ß-blockers (77.9%), EBL (59.8%), EBL+ß-blockers+isosorbide-5-mononitrate (52.7%), EBL+ß-blockers (51.4%), EIS (34.2%), ß-blockers+isosorbide-5-mononitrate (23.7%), ß-blockers (20.8%), and placebo (0.8%). In reducing rebleeding-related mortality, TIPS SUCRA (87.2%) was more efficacious than EBL+EIS (83.5%), EIS (47.9%), EBL+ß-blockers (47.4%), ß-blockers (41.8%), EBL (34.5%), and placebo (7.6%). In reducing overall mortality, TIPS SUCRA (81.1%) was superior to EBL+EIS (68.9%), EIS+ß-blockers (59.2%), EBL+ß-blockers (55.4%), EIS (48.8%), EBL (48.7%), ß-blockers (34.2%), placebo (3.6%). CONCLUSIONS: TIPS was more effective in reducing the incidence of cirrhosis EV rebleeding, rebleeding-related mortality, and overall mortality in cirrhosis. Combined with the above results, TIPS is more likely to be recommended as a secondary prophylaxis intervention for EV in cirrhosis.

Silencing LncRNA-DANCR attenuates inflammation and DSS-induced endothelial injury through miR-125b-5p.

BACKGROUND: LncRNA-DANCR is involved in inflammation and acts as a major contributor to colon cancer. The effects and mechanism of LncRNA-DANCR were first investigated in a DSS-induced colitis model in vivo and vitro. MATERIAL AND METHODS: Sprague-Dawley rats were given DSS to induce the colitis model. TNF-α, IL-1ß, IL-6 levels and expression of intestinal adhesion proteins ZO-1 and MUC2 in colon tissues and DSS-induced NCM460 cells were measured using corresponding kits. A hematoxylin and eosin (H&E) staining assay was performed to evaluate colon tissue pathology conditions. Protein expression levels in DSS-induced NCM460 cells were evaluated by Western blotting, and cell apoptosis was detected using a TUNEL assay. Gene levels in DSS-induced NCM460 cells were evaluated by PCR. The StarBase online tool was used to predict the LncRNA-DANCR target. The LncRNA-DANCR target was verified using a luciferase reporter assay. RESULTS: LncRNA-DANCR was up-regulated in DSS-induced groups of rats. TNF-α, IL-1ß and IL-6 expression was significantly increased in DSS-induced groups of rats and cells. Zo-1 and MUC2 expression levels were decreased in DSS-induced groups of rats. Silencing LncRNA-DANCR reduced inflammation, cell apoptosis and up-regulated ZO-1, MUC2 and Claudin-1 in DSS-induced cells. MiR-125b-5p was the downstream LncRNA-DANCR target. All LncRNA-DANCR effects in the colitis model were reversed by the miR-125b-5p inhibitor. CONCLUSION: LncRNA-DANCR/miR-125b-5p, which may act as a regulatory axis in inflammation, apoptosis and barrier function dysregulation, can provide an essential reference for the development of new drugs in colitis treatment.