Contribution of NOTCH signaling pathway along with TNF-α in the intestinal inflammation of ulcerative colitis

Mahsa Ghorbaninejad; Raheleh Heydari; Parvaneh Mohammadi; Shabnam Shahrokh; Mehrdad Haghazali; Binazir Khanabadi; Anna Meyfour

Contribution of NOTCH signaling pathway along with TNF-α in the intestinal inflammation of ulcerative colitis

Gastroenterol Hepatol Bed Bench. 2019;12(Suppl1):S80-S86.

Authors

Mahsa Ghorbaninejad¹, Raheleh Heydari¹, Parvaneh Mohammadi¹, Shabnam Shahrokh¹, Mehrdad Haghazali², Binazir Khanabadi³, Anna Meyfour³

Affiliations

¹ Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
² Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran.
³ Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

PMID: 32099606
PMCID: PMC7011072

Abstract

Aim: The aim of this study was to determine gene expression levels of TNF-α, NOTCH1, and HES1 in patients with UC.

Background: Intestinal inflammation and epithelial injury are the leading actors of inflammatory bowel disease (IBD), causing an excessive expression of pro-inflammatory cytokines such as TNF-α. Also, target genes of NOTCH signaling are involved in the regulation of intestinal homeostasis. Previous studies have demonstrated that TNF-α increases in ulcerative colitis (UC) patients, but the relationship between TNF-α and NOTCH signaling pathway in UC etiopathology needs further study.

Methods: Twelve active UC patients and twelve healthy controls were enrolled in this study. RNA was extracted and the mRNA expression levels of TNF-α, NOTCH1, and HES1 were examined using real-time PCR analyses. Further, transcriptome data deposited in Gene Expression Omnibus (GEO) database were analyzed to detect the differential expression of TNF superfamily and NOTCH1 gene in IBD patients. Finally, the interaction of TNF-α and NOTCH signaling was obtained from The SIGnaling Network Open Resource 2.0 (SIGNOR 2.0) database.

Results: The transcription levels of TNF-α, NOTCH1, and HES1 genes were significantly elevated in UC patients compared with control (p < 0.05). In addition, GEO results confirmed our expression results. SIGNOR analysis showed that TNF-α interacts with NOTCH signaling components.

Conclusion: Based on our data, we observed that NOTCH1 and HES1 in co-operation of TNF-α, may play an important role in pathogenesis of UC. The members of NOTCH signaling pathway can be ideal candidates to target the therapy of IBD.

Keywords: HES1; NOTCH signaling; TNF-α; Ulcerative colitis.