miR-511 Deficiency Protects Mice from Experimental Colitis by Reducing TLR3 and TLR4 Responses via WD Repeat and FYVE-Domain-Containing Protein 1

Abstract

Antimicrobial responses play an important role in maintaining intestinal heath. Recently we reported that miR-511 may regulate TLR4 responses leading to enhanced intestinal inflammation. However, the exact mechanism remained unclear. In this study we investigated the effect of miR-511 deficiency on anti-microbial responses and DSS-induced intestinal inflammation. miR-511-deficient mice were protected from DSS-induced colitis as shown by significantly lower disease activity index, weight loss and histology scores in the miR-511-deficient group. Furthermore, reduced inflammatory cytokine responses were observed in colons of miR-511 deficient mice. In vitro studies with bone marrow-derived M2 macrophages showed reduced TLR3 and TLR4 responses in miR-511-deficient macrophages compared to WT macrophages. Subsequent RNA sequencing revealed Wdfy1 as the potential miR-511 target. WDFY1 deficiency is related to impaired TLR3/TLR4 immune responses and the expression was downregulated in miR-511-deficient macrophages and colons. Together, this study shows that miR-511 is involved in the regulation of intestinal inflammation through downstream regulation of TLR3 and TLR4 responses via Wdfy1.

Low miR 511-5p Expression as a Potential Predictor of a Poor Nutritional Status in Head and Neck Cancer Patients Subjected to Intensity-Modulated Radiation Therapy

“…According to our results, miR-511-3p might be related to both nutritional deficiencies (evaluated according to SGA and CWL criteria) and advancement of disease (T tumor stage). Thus, it is in accordance with the previously described versatility of miRNAs [28][29][30][31][32].…”

“…It is known that the MRC1 gene is expressed by dendritic cells (DCs) and macrophages. High levels of the product of the MRC1 gene were noted in anti-inflammatory, wound healing, and tumor-associated macrophages [32]. Moreover, it has been demonstrated, that MRC1 expression is downregulated by INF-γ and upregulated by IL-4 and IL-13 [33].…”

“…On the other hand, overexpression of miR-511-3p causes decreased activation of PPARγ and increased production of pro-inflammatory cytokines [34][35][36]. Other research suggests that human miR-511 also has a role in TLR4 signaling, although the specific mechanism remains unknown [32]. Moreover, based on information available in miRNA databases (Target Scan 7.2, miRDBase), it can be predicted that studied miRNA could potentially participate in the regulation of a number of genes involved in metabolism (IGF1R, IGF2, and IGF2BP1) or inflammation (TAB1, TAB3, LTBP1, TRAF1, IL6ST, IL7R, IL17RA, IL17RD, IL1R, and TLR4).…”

Cell-type-specific characterization of miRNA gene dynamics in immune cell subpopulations during aging and atherosclerosis disease development at single-cell resolution

“…S4A, Table S4). Among immunomodulatory miRNAs with potential to aggravate tissue inflammation, we noted increased expression of mmu-mir-511 42 driven by nodes 2-8 (Fig. 4A).…”

The Enticing Path of miR Therapeutics: Difficult but Not without Prospects

“…This promotes intestinal inflammation by regulating the TLR4 responses, but the mechanism remains unknown. Rahman et al show that the inflammatory effect of miR-511 is mediated by regulation of TLR3/4 response via wdfy1 [7].…”