Roles of Macrophage Polarization and Macrophage-Derived miRNAs in Pulmonary Fibrosis

Abstract

This mini-review summarizes the current evidence for the role of macrophage activation and polarization in inflammation and immune response pertinent to interstitial lung disease, specifically pulmonary fibrosis. In the fibrosing lung, the production and function of inflammatory and fibrogenic mediators involved in the disease development have been reported to be regulated by the effects of polarized M1/M2 macrophage populations. The M1 and M2 macrophage phenotypes were suggested to correspond with the pro-inflammatory and pro-fibrogenic signatures, respectively. These responses towards tissue injury followed by the development and progression of lung fibrosis are further regulated by macrophage-derived microRNAs (miRNAs). Besides cellular miRNAs, extracellular exosomal-miRNAs derived from M2 macrophages have also been proposed to promote the progression of pulmonary fibrosis. In a future perspective, harnessing the noncoding miRNAs with a key role in the macrophage polarization is, therefore, suggested as a promising therapeutic strategy for this debilitating disease.

Keywords: M1/M2 polarization; MicroRNAs; exosomes; macrophage plasticity; pulmonary fibrosis.

Figure 1

M1 macrophage and M2 macrophage polarization during the development of pulmonary fibrosis. *Increased cellular factors include proliferation, α-smooth muscle actin (α-SMA), matrix factors, collagen, growth factors and cytokines. **Dysregulated genetic factors include upregulated miR-21 and miR-155 and down-regulated Let-7i, miR-107, mir-126, miR-140 and miR-511. Figure created with BioRender. AIM2, absent in melanoma 2; ARG1, Arginase 1; Fizz1/RETNLB, resistin like beta; Ym1/Chil3, chitinase-like 3.