Tectorigenin regulates migration, invasion, and apoptosis in dexamethasone‐induced human airway epithelial cells through up‐regulating miR‐222‐3p

Abstract

Glucocorticoids (GCs) can effectively control airway inflammation, but can also cause airway epithelial injury. Tectorigenin, a type of isoflavone isolated from various medicinal plants, has hypolipidemic activity, hepatoprotective, and antioxidant effects. We aimed to investigate whether Tectorigenin can repair GCs‐induced airway epithelial injury. Airway epithelial cell line (9HTE cells) were treated with dexamethasone (Dex), Tectorigenin, or further transfected, then cell viability, migration, and invasion were examined by Cell Counting Kit (CCK‐8), wound healing, and Transwell assays. The expressions of potential miRNAs related to the effect of Tectorigenin were detected by quantitative polymerase chain reaction (qPCR). Expressions of poptosis‐related proteins Bcl‐2‐associated protein‐X (Bax), B‐cell lymphoma‐2 (Bcl‐2), Cleaved Caspase‐3, and related to Mitorgen‐activated protein kinase (MAPK) signaling pathway serine/threonine kinase (Raf1), extracellular signal‐regulated kinase kinase 1/2 (MEK1/2), and extracellular signal‐regulated kinase 1/2 (ERK1/2) were detected by Western blot. Dex inhibited the cell viability, migration and invasion by promoting Bax and Cleaved Caspase‐3 expressions (p <.001) and by inhibiting the expressions of Bcl‐2 and miR‐222‐3p (p <.001). Then, 10 μmol/L Tectorigenin itself did not affect cell viability but could inhibit the effect of Dex on cell viability, migration, and invasion. Tectorigenin up‐regulated the expressions of miR‐222‐3p, Bcl‐2, p‐Raf1, p‐MEK1/2, and p‐ERK1/2 (p <.01), but down‐regulated the expressions of Bax and Cleaved Caspase‐3 (p <.05) in Dex‐induced cells. MiR‐222‐3p inhibitor reversed the antagonistic effect of Tectorigenin on Dex. The study demonstrates that Tectorigenin inhibits apoptosis of Dex‐induced 9HTE cells by up‐regulating the expression of miR‐222‐3p, which involves with the MAPK pathway.

Tectorigenin suppresses the viability of gastric cancer cells in vivo and in vitro

“…Tec alleviated intrahepatic cholestasis by suppressing hepatic inflammation and bile accumulation by mediating the PPARγ pathway (Xiang et al, 2021). Tec also mediates the motility and apoptosis in dexamethasone-stimulated airway epithelial cells via activating miR-222-3p (Qian, Xiao, & Li, 2021). Here, we noticed that Tec inhibited gastric cancer cell proliferation.…”

“…Tec plays a crucial role in combating tumor progression. Tec could ablate the inflammation-induced EMT in a human lung carcinoma co-culture model, suggesting the anti-tumor activity of Tec (Qian et al, 2021). Tec could also suppress glioblastoma cell proliferation by stimulating G0/G1 cell cycle arrest (Yeh et al, 2020).…”

Tectorigenin: A Review of Its Sources, Pharmacology, Toxicity, and Pharmacokinetics

“…Tectorigenin was regarded as an interventional strategy by inhibiting respiratory dysfunction and death in respiratory diseases. Several studies have illustrated the protective effect of tectorigenin in respiratory disorders, including asthma, airway epithelial injury, and pulmonary fibrosis [24,154,155]. Asthma is a common chronic disease characterized by variable respiratory symptoms and airflow limitation [156].…”

“…It was demonstrated that tectorigenin regulated migration, invasion, and apoptosis of human airway epithelial cells in the treatment of glucocorticoids. Mechanistically, tectorigenin enhanced miR-222-3p expression and inhibited the MAPK pathway, thus protecting the airway epithelium [154]. Idiopathic pulmonary fibrosis is also a chronic, progressive pulmonary disease characterized by the anomalous accumulation of fibrotic tissue in the lung's parenchyma [157].…”