imprint:
[Erscheinungsort nicht ermittelbar]: [Verlag nicht ermittelbar], 2019
Language:
English
Identifier:
Origination:
University thesis:
Dissertation, 2019
Footnote:
Description:
Peroxiredoxins (PRDXs) are conserved antioxidant enzymes protecting from oxidative damages and involved in redox and inflammatory signaling. Among the six mammalian PRDXs, PRDX5 expression is highly variable, e.g. upon inflammatory response, although PRDX5 presents characteristics of a housekeeping gene. Reports accumulate about microRNAs (miRNA) contribution to the control of gene basal expression levels and miRNAs regulating redox signaling and innate immunity. Therefore, this work addressed i) human and mouse miRNAs role in PRDX5 expression control and PRDX5 subcellular targeting and ii) human and mouse PRDX5 expression modulations under pro-inflammatory conditions. First, luciferase reporter assays revealed that eleven human miRNAs, among fifteen miRNAs selected in silico and based on data of the literature, target human PRDX5 3'UTR. However, among the selected miRNAs only two mouse homologous were able to regulate mouse PRDX5 expression. In human Saos-2 cells, anti-mir-92 and -181 increased PRDX5 expression and in eight human cell lines, mir-92a and -181d expression levels were correlated to PRDX5 expression. Second, the use of synthetic miRNAs targeting PRDX5 5' region shows that miRNAs may not modulate PRDX5 distribution in human cell lines. Third, pro-inflammatory mediators, e.g. LPS, upregulated PRDX5 only in mouse phagocytic cell lines. Moreover, in the mouse microglial BV2 cell line, PRDX5 overexpression increased IL-1β release. In conclusion i) miRNAs targeting PRDX5 are different in human and mouse, ii) selected miRNAs do not modulate PRDX5 subcellular targeting, iii) regulation of PRDX5 expression upon inflammatory response depends on the cell type, the species and the stimuli and iv) PRDX5, acting as a damage associated molecular pattern (DAMP), could promote IL-1β release via a positive feed-back loop. Born on the 17th of October 1990, grown up in Halanzy, Gaume, Belgium. Master in Biochemistry, Molecular and Cellular Biology in June 2013. ; (SC - Sciences) -- UCL, 019