MicroRNA-31-3p Is Involved in Substance P (SP)-Associated Inflammation in Human Colonic Epithelial Cells and Experimental Colitis.

MicroRNA-31-3p Is Involved in Substance P (SP)-Associated Inflammation in Human Colonic Epithelial Cells and Experimental Colitis. Am J Pathol. 2017 Dec 15;: Authors: Fang K, Law IKM, Padua D, Sideri A, Huang V, Kevil CG, Iliopoulos D, Pothoulakis C Abstract Substance P (SP) mediates colitis. SP signaling regulates the expression of several microRNAs (miRNAs), including miR-31-3p, in human colonocytes. However, the role of miR-31-3p in colitis and the underlying mechanisms has not been elucidated. We performed real time PCR analysis of miR-31-3p expression in human colonic epithelial cells overexpressing neurokinin-1 receptor (NCM460 NK-1R) in response to SP stimulation and in NCM460 cells following interleukin (IL)-6, IL8, tumor necrosis factor (TNF)-α, and interferon-γ exposure. Functions of miR-31-3p were tested in NCM460-NK-1R cells and the TNBS and DSS models of colitis. Targets of miRNA-31-3p were confirmed by Western blot and luciferase reporter assays. JNK inhibition decreased SP-induced miR-31-3p expression. MiR-31-3p expression was increased in both TNBS- and DSS-induced colitis and human colonic biopsies from ulcerative colitis, compared to controls. Intracolonic administration of a miR-31-3p chemical inhibitor exacerbated TNBS and DSS-induced colitis and increased colonic TNF-α, CXCL10, and CCL2 mRNA expression. Conversely, overexpression of miR-31-3p ameliorated the severity of DSS-induced colitis. Bioinformatic, luci...
Source: The American Journal of Pathology - Category: Pathology Authors: Tags: Am J Pathol Source Type: research