Arsenic trioxide prevents rat pulmonary fibrosis via miR-98 overexpression

Aims This study aimed to investigate the pathogenesis mechanisms of bleomycin (BLM)-induced pulmonary fibrosis (PF) in Sprague–Dawley rats and explore the anti-fibrotic role of arsenic trioxide (As2O3) in preventing PF. Main methods Intratracheal instillation of BLM was performed to establish PF rat models. The treatment group was treated with As2O3 (0.4mg/kg/day). Morphological changes were observed by hematoxylin–eosin and Masson staining. Related proteins were determined by immunohistochemistry, immunofluorescence, and Western blot. MicroRNA detection was performed by quantitative real-time polymerase chain reaction. Key findings As a novel miRNA in PF, miR-98 decreased in the fibrotic lung tissues. Based on microRNA analysis software, we found that Stat3-3′-UTR is targeted by miR-98. Then, we found that Stat3 was activated with PF development and the expression of Stat3 and p-Stat3 was significantly increased in BLM-induced PF at day 28 compared with saline-treated rats. Our results showed that both Stat3 and p-Stat3 were significantly decreased in miR-98-treated A549 cells compared with that in mu-98-treated cultures or untreated controls. The fibrotic marker α-SMA was upregulated, whereas E-cadherin was inhibited in fibrotic lung tissues. The ratio of apoptotic factors Bax/Bcl-2 increased with the development of fibrosis. Furthermore, As2O3 treatment prevented lung interstitial thickening and inhibited the collagen type I and hydroxyproline, thereby preventing the development of PF. As2O3 also significantly down-regulated α-SMA but increased E-cadherin and miR-98 levels. Significance The study revealed that arsenic trioxide prevented rat PF by up-regulation of miR-98 and inhibition of its downstream Stat3 signals.