LncRNA PTPRE-AS1 modulates M2 macrophage activation and inflammatory diseases by epigenetic promotion of PTPRE

Xiao Han, Saihua Huang, Ping Xue, Jinrong Fu, Lijuan Liu, Caiyan Zhang, Lan Yang, Li Xia, Licheng Sun, Shau Ku Huang, Yufeng Zhou

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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.

Original languageEnglish
Article numbereaax9230
JournalScience Advances
Volume5
Issue number12
DOIs
Publication statusPublished - Dec 11 2019
Externally publishedYes

ASJC Scopus subject areas

  • Physics and Astronomy (miscellaneous)
  • General

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    Han, X., Huang, S., Xue, P., Fu, J., Liu, L., Zhang, C., Yang, L., Xia, L., Sun, L., Huang, S. K., & Zhou, Y. (2019). LncRNA PTPRE-AS1 modulates M2 macrophage activation and inflammatory diseases by epigenetic promotion of PTPRE. Science Advances, 5(12), [eaax9230]. https://doi.org/10.1126/sciadv.aax9230