Abstract
LncRNAs play an indispensable role in the process of M1 macrophage via
regulating the development of macrophages and their responses to
bacterial pathogens and viral infections. However, there are few studies
on the lncRNA-mediated functions and regulatory mechanisms of M2
macrophage polarization. In this study, we found a number of
differentially expressed lncRNAs between human monocyte derived M0 and
M2 macrophages according to array analysis and qRT-PCR validation. The
lncRNA RP11-389C8.2 (we named lnc-M2 in this study) was observed to be
highly expressed in M2 macrophages. In Situ Localization and
Quantification Analysis showed that lnc-M2 was expressed in the nucleus
and cytosolic compartments of M2 macrophages. Notably, lnc-M2 knockdown
enhanced the phagocytic ability of M2 macrophages. Ulteriorly, the
results of RNA-Protein interaction experiments indicated that protein
kinase A (PKA) was a lnc-M2 associated RNA-binding protein (RBP).
Western blot showed that p-CREB, a well-known key downstream
transcription factor of PKA, was lowly phosphorylated in
lnc-M2-silencing M2 macrophages. Furthermore, we found that
transcriptional factor STAT3 promoted lnc-M2 transcription along with
the up-regulation of epigenetic histone modification markers at the
lnc-M2 promoter locus, indicating that STAT3 activated lnc-M2 and
eventually facilitated the process of M2 macrophage differentiation via
the PKA/CREB pathway. Collectively, our date provide evidence that the
transcription factor STAT3 can promote the transcription of lnc-M2 and
facilitated the process of M2 macrophage differentiation via the
PKA/CREB pathway. This study highlights a novel mechanism underlying the
M2 macrophage differentiation.