Semaphorin 3E regulates apoptosis in the intestinal epithelium during the development of colitis

Autor: Abdoulaye Diarra, Hayam Hussein, Nour Eissa, Omar Elgazzar, Jean-Eric Ghia, Abdelilah S. Gounni, Charles N. Bernstein
Rok vydání: 2019
Předmět:
Zdroj: Biochemical Pharmacology. 166:264-273
ISSN: 0006-2952
DOI: 10.1016/j.bcp.2019.05.029
Popis: Semaphorin 3E (SEMA3E) has emerged as an axon-guiding molecule that regulates various biological processes including the immune responses and apoptosis. However, its role in the pathophysiology of colitis remains elusive. We investigated the role of SEMA3E in intestinal epithelial cells (IECs) activation, using biopsies from patients with active ulcerative colitis (UC), a mouse model of UC, and an in-vitro model of intestinal mucosal healing. In this study, we confirmed that the mRNA level of SEMA3E is reduced significantly in patients with UC and demonstrated a negative linear association between SEMA3E mRNA and p53-associated genes. In mice, genetic deletion of Sema3e resulted in an increase onset and severity of colitis, p53-associated genes, apoptosis, and IL-1beta production. Recombinant SEMA3E treatment protected against colitis and decreased these effects. Furthermore, in stimulated epithelial cells, recombinant SEMA3E treatment enhanced wound healing, resistance to oxidative stress and decreased apoptosis and p53-associated genes. Together, these findings identify SEMA3E as a novel regulator in intestinal inflammation that regulates IECs apoptosis and suggest a potential novel approach to treat UC.
Databáze: OpenAIRE
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