MicroRNA-21 mediates bone marrow mesenchymal stem cells protection of radiation-induced lung injury during the acute phase by regulating polarization of alveolar macrophages.

ABSTRACT

BACKGROUND: Radiation-induced lung injury (RILI) often occurs in patients with non-small cell lung cancer (NSCLC) after radiotherapy, and the prognosis of patients with RILI is usually poor. This work plan to investigate the expression patterns of microRNA-21(miR-21) in NSCLC patients with RILI and the protective effects of miR-21 over-expressed bone marrow mesenchymal stem cells (BMSCs) against RILI in rat model. METHODS: MiR-21 expressions were determined in both serum samples and bronchoalveolar lavage fluid (BALF) samples from NSCLC patients after radiation therapy. The correlation between miR-21 expression and the follow-up clinical characterizations were determined. Further, miR-21 over-expressed BMSCs were transplanted into RILI rats and the protective effects were evaluated. BMSCs and alveolar macrophages (AMs) were co-cultured in vitro and the macrophage M1 polarization markers were determined by ELISA and qRT-PCR assays. RESULTS: Expression of miR-21 was significantly increased in NSCLC patients with RILI compared with control group, especially before or at 4 weeks after radiation therapy commenced. The miR-21 levels were highly correlated with IL-12, TNF-α, and IL-6 expressions and the severity of RILI. Animal based experiments demonstrated that BMSCs treatment had a remarkable effect on alleviating alveolitis in RILI rats, and miR-21 over-expression could enhance this effect significantly. Cell based experiments demonstrated that BMSCs notably inhibited M1 polarization of AMs and this inhibition is in a miR-21 dependent manner. CONCLUSIONS: These results indicated that BMSCs could blocked the proinflammatory pathway of macrophage through miR-21 over-expression, thus could be a potential therapeutic strategy for RILI.