TY - JOUR
T1 - LncRNA PTPRE-AS1 modulates M2 macrophage activation and inflammatory diseases by epigenetic promotion of PTPRE
AU - Han, Xiao
AU - Huang, Saihua
AU - Xue, Ping
AU - Fu, Jinrong
AU - Liu, Lijuan
AU - Zhang, Caiyan
AU - Yang, Lan
AU - Xia, Li
AU - Sun, Licheng
AU - Huang, Shau Ku
AU - Zhou, Yufeng
N1 - Publisher Copyright:
Copyright © 2019 The Authors
PY - 2019/12/11
Y1 - 2019/12/11
N2 - Long noncoding RNAs (lncRNAs) are important regulators of diverse biological processes; however, their function in macrophage activation is undefined. We describe a new regulatory mechanism, where an unreported lncRNA, PTPRE-AS1, targets receptor-type tyrosine protein phosphatase ε (PTPRE) to regulate macrophage activation. PTPRE-AS1 was selectively expressed in IL-4–stimulated macrophages, and its knockdown promoted M2 macrophage activation via MAPK/ERK 1/2 pathway. In vivo, PTPRE-AS1 deficiency enhanced IL-4–mediated M2 macrophage activation and accelerated pulmonary allergic inflammation while reducing chemical-induced colitis. Mechanistically, PTPRE-AS1bound WDR5 directly, modulating H3K4me3 of the PTPRE promoter to regulate PTPRE-dependent signaling during M2 macrophage activation. Further, the expression of PTPRE-AS1 and PTPRE was significantly lower in peripheral blood mononuclear cells from patients with allergic asthma. These results provide evidence supporting the importance of PTPRE-AS1 in controlling macrophage function and the potential utility of PTPRE-AS1 as a target for controlling inflammatory diseases.
AB - Long noncoding RNAs (lncRNAs) are important regulators of diverse biological processes; however, their function in macrophage activation is undefined. We describe a new regulatory mechanism, where an unreported lncRNA, PTPRE-AS1, targets receptor-type tyrosine protein phosphatase ε (PTPRE) to regulate macrophage activation. PTPRE-AS1 was selectively expressed in IL-4–stimulated macrophages, and its knockdown promoted M2 macrophage activation via MAPK/ERK 1/2 pathway. In vivo, PTPRE-AS1 deficiency enhanced IL-4–mediated M2 macrophage activation and accelerated pulmonary allergic inflammation while reducing chemical-induced colitis. Mechanistically, PTPRE-AS1bound WDR5 directly, modulating H3K4me3 of the PTPRE promoter to regulate PTPRE-dependent signaling during M2 macrophage activation. Further, the expression of PTPRE-AS1 and PTPRE was significantly lower in peripheral blood mononuclear cells from patients with allergic asthma. These results provide evidence supporting the importance of PTPRE-AS1 in controlling macrophage function and the potential utility of PTPRE-AS1 as a target for controlling inflammatory diseases.
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U2 - 10.1126/sciadv.aax9230
DO - 10.1126/sciadv.aax9230
M3 - Article
C2 - 31844669
AN - SCOPUS:85076703063
SN - 0019-5596
VL - 5
JO - Science Advances
JF - Science Advances
IS - 12
M1 - eaax9230
ER -