迷迭香酸通过miR-19b-3p减轻ROS/MYPT1/TGFβ1信号传导来预防辐射诱导的肺纤维化。
Rosmarinic Acid Prevents Radiation-Induced Pulmonary Fibrosis Through Attenuation of ROS/MYPT1/TGFβ1 Signaling Via miR-19b-3p.
作者信息
Zhang Tingting, Ma Shanshan, Liu Chang, Hu Kai, Xu Meng, Wang Rensheng
机构信息
Department of Radiation Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
出版信息
Dose Response. 2020 Oct 19;18(4):1559325820968413. doi: 10.1177/1559325820968413. eCollection 2020 Oct-Dec.
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.
辐射所致肺纤维化的机制仍不清楚。由于迷迭香酸(RA)具有抗氧化和抗炎特性,我们旨在评估RA对X射线诱导的肺损伤的影响。雄性大鼠在接受15 Gy X射线照射前7天给予RA(30、60或120 mg/kg)。在此,我们发现RA可降低X射线诱导的炎症相关因子的表达以及活性氧水平。RA可下调核因子κB(NF-κB)的磷酸化。我们发现肺部接受过放疗的胸段肿瘤患者的微小RNA-19b-3p(miR-19b-3p)水平较低。此外,我们提供证据表明miR-19b-3p靶向肌球蛋白磷酸酶靶向亚基1(MYPT1),且RA通过上调miR-19b-3p减弱RhoA/Rock信号传导,从而抑制纤维化。总之,RA可能是缓解胸段肿瘤放疗所致肺纤维化的有效药物。