Rosmarinic Acid Prevents Radiation-Induced Pulmonary Fibrosis Through Attenuation of ROS/MYPT1/TGFβ1 Signaling Via miR-19b-3p.

Abstract

The mechanism of pulmonary fibrosis caused by irradiation remains obscure. Since rosmarinic acid (RA) have anti-oxidant and anti-inflammatory properties, we aimed to evaluate the effect of RA on the X-ray-induced lung injury. Male rats received RA (30, 60, or 120 mg/kg) 7 days before 15 Gy of X-ray irradiation. Here, we showed that RA reduced X-ray-induced the expression of inflammatory related factors, and the level of reactive oxygen species. RA down-regulated the phosphorylation of nuclear factor kappa-B (NF-κB). We found that thoracic tumor patients whose lung regions received radiation showed lower level of microRNA-19b-3p (miR-19b-3p). Furthermore, we provided evidence that miR-19b-3p targets myosin phosphatase target subunit 1 (MYPT1), and RA attenuated RhoA/Rock signaling through upregulating miR-19b-3p, leading to the inhibition of fibrosis. In conclusion, RA may be an effective agent to relieve the pulmonary fibrosis caused by radiotherapy of thoracic tumor.