Tetrandrine Suppresses The Tgf-Beta 1-Induced Proliferation And Migration Of Airway Smooth Muscle Cells Using The Nrf2-Are Signaling Pathway

Airway smooth muscle cell (ASMCs) proliferation and migration facilitates airway remodeling in asthma. Tetrandrine is a major compound derived from Stephania tetrandra S. Moore that has anti allergic activity. This study aimed to investigate the effect of tetrandrine on ASMCs' proliferation and migration and its underlying mechanism. Transforming growth factor-beta 1 (TGF-beta 1)-treated ASMCs were cultured for analyses in vitro. Cell proliferation was measured using an MTT assay. Cytotoxicity was investigated using lactate dehydrogenase (LDH) release and apoptosis. The cell cycle distribution was determined using flow cytometry. Cell migration was measured using a trans-well assay. The levels of reactive oxygen species (ROS) production, superoxide dismutase (SOD) activity, glutathione (GSH) activity, and malonaldehyde (MDA) content were quantified using a specific kit. The levels of the extracellular matrix (ECM)-related proteins were detected by western blot. The nuclear factor E2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway was evaluated using western blot. Tetrandrine inhibited TGF-beta 1-caused proliferation and migration in ASMCs. Tetrandrine regulated the cell cycle distribution but did not affect the LDH release or the apoptosis upon the stimulation of TGF-beta 1. Tetrandrine suppressed TGF-beta 1-induced oxidant stress and ECM in the ASMCs. Tetrandrine promoted the Nrf2-ARE pathway, and the knockdown of Nrf2 weakened the function of tetrandrine on the proliferation, migration, oxidant stress, and ECM. In conclusion, Tetrandrine represses proliferation and migration in TGF-beta 1-treated ASMCs by inhibiting oxidant stress and ECM using the Nrf2-ARE pathway, indicating a novel avenue for the therapy of asthma airway remodeling.