Down-regulation of RTEL1 Improves M1/M2 Macrophage Polarization by Promoting SFRP2 in Fibroblasts-derived Exosomes to Alleviate COPD

Chronic obstructive pulmonary disease (COPD) is a common chronic respiratory disease worldwide. Macrophage polarization plays a substantial role in the pathogenesis of COPD. This study is aimed to explore the regulatory mechanism of regulator of telomere elongation 1 (RTEL1) in COPD. COPD model mouse was conducted by cigarette smoke (CS). The pathological features of lung in mice were observed by histological staining. After extracting exosomes, macrophages were co-cultured with fibroblasts-derived exosomes. Then, the effects of RTEL1 and exosomal secreted frizzled-related protein 2 (SFRP2) on macrophage proliferation, inflammation, apoptosis, and M1, M2 macrophage polarization (iNOS and CD206) were evaluated by cell counting kit-8, EdU assay, enzyme-linked immuno sorbent assay, and western blotting, respectively. CS-induced COPD model mouse was successfully constructed. Through in vitro experiments, knockdown of RTEL1 inhibited macrophage proliferation, inflammation (MMP9, IL-1β and TNF-α), and promoted apoptosis (Bax, cleaved-caspase3, Bcl-2) in CS extract-induced lung fibroblasts. Meanwhile, RTEL1 knockdown promoted M1 and suppressed M2 macrophage polarization in COPD. Additionally, silencing SFRP2 in fibroblasts-derived exosomes reversed the effects of RTEL1 knockdown on proliferation, inflammation, apoptosis, and M1, M2 macrophage polarization. Collectively, down-regulation of RTEL1 improved M1/M2 macrophage polarization by promoting SFRP2 in fibroblasts-derived exosomes to alleviate CS-induced COPD.