Ligustrazin increases lung cell autophagy and ameliorates paraquat-induced pulmonary fibrosis by inhibiting PI3K/Akt/mTOR and hedgehog signalling via increasing miR-193a expression
机构：[1]Department of Emergency, the First Affiliated Hospital of Kunming Medical University, 295 Xichang Road, Kunming 650032, Yunan, People’s Republic of China.内科科室急诊医学科昆明医科大学附属第一医院[2]Emergency Intensive Care Unit, the Second Affiliated Hospital of Kunming Medical University, Kunming 650106, China.[3]Skin Disease Prevention Institute of Wenshan Zhuang and Miao autonomous prefecture, Wenshan 655500, China.[4]Intensive Care Unit, the Yan-an Affiliated Hospital of Kunming Medical University, Kunming 650106, China.[5]Department of Thoracic Surgery, People’s Hospital of Fuyuan County, Qujing 655500, China.
BackgroundReactive oxygen species (ROS) levels largely determine pulmonary fibrosis. Antioxidants have been found to ameliorate lung fibrosis after long-term paraquat (PQ) exposure. The effects of antioxidants, however, on the signalling pathways involved in PQ-induced lung fibrosis have not yet been investigated sufficiently. Here, we examined the impacts of ligustrazin on lung fibrosis, in particular ROS-related autophagy and pro-fibrotic signalling pathways, using a murine model of PQ-induced lung fibrosis.MethodsWe explored the effects of microRNA-193 (miR-193a) on Hedgehog (Hh) and PI3K/Akt/mTOR signalling and oxidative stress in lung tissues. Levels of miR-193a, protein kinase B (Akt), phosphoinositide 3-Kinase (PI3K), ceclin1, mammalian target of rapamycin (mTOR), sonic hedgehog (SHH), myosin-like Bcl2 interacting protein (LC3), smoothened (Smo), and glioma-associated oncogene-1 (Gli-1) mRNAs were determined with quantitative real-time PCR. Protein levels of PI3K, p-mTOR, p-Akt, SHH, beclin1, gGli-1, LC3, smo, transforming growth factor-1 (TGF-1), mothers against DPP homologue-2 (Smad2), connective tissue growth factor (CTGF), collagen I, collagen III, -smooth muscle actin (-SMA) nuclear factor erythroid 2p45-related factor-2 (Nrf2), and p-Smad2 were detected by western blotting. In addition, -SMA, malondialdehyde, ROS, superoxide dismutase (SOD), oxidised and reduced glutathione, hydroxyproline, and overall collagen levels were identified in lung tissues using immunohistochemistry.ResultsLong-term PQ exposure blocked miR-193a expression, reduced PI3K/Akt/mTOR signalling, increased oxidative stress, inhibited autophagy, increased Hh signalling, and facilitated the formation of pulmonary fibrosis. Ligustrazin blocked PI3K/Akt/mTOR and Hh signalling as well as reduced oxidative stress via increasing miR-193a expression and autophagy, all of which reduced pulmonary fibrosis. These effects of ligustrazin were accompanied by reduced TGF-1, CTGF, and Collagen I and III expression.ConclusionsLigustrazin blocked PQ-induced PI3K/Akt/mTOR and Hh signalling by increasing miR-193a expression, thereby attenuating PQ-induced lung fibrosis.
基金：
This research was supported by Yunnan Applied Basic Research Project-
Union Foundation of China (Grant No. 2017FE468 (− 032)).
第一作者机构：[1]Department of Emergency, the First Affiliated Hospital of Kunming Medical University, 295 Xichang Road, Kunming 650032, Yunan, People’s Republic of China.
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推荐引用方式(GB/T 7714)：
Ming-wei Liu,Mei-xian Su,Deng-yun Tang,et al.Ligustrazin increases lung cell autophagy and ameliorates paraquat-induced pulmonary fibrosis by inhibiting PI3K/Akt/mTOR and hedgehog signalling via increasing miR-193a expression[J].BMC PULMONARY MEDICINE.2019,19:doi:10.1186/s12890-019-0799-5.
APA：
Ming-wei Liu,Mei-xian Su,Deng-yun Tang,Li Hao,Xiang-Han Xun&Yun-qiao Huang.(2019).Ligustrazin increases lung cell autophagy and ameliorates paraquat-induced pulmonary fibrosis by inhibiting PI3K/Akt/mTOR and hedgehog signalling via increasing miR-193a expression.BMC PULMONARY MEDICINE,19,
MLA：
Ming-wei Liu,et al."Ligustrazin increases lung cell autophagy and ameliorates paraquat-induced pulmonary fibrosis by inhibiting PI3K/Akt/mTOR and hedgehog signalling via increasing miR-193a expression".BMC PULMONARY MEDICINE 19.(2019)
