TGF-β1 induces airway smooth muscle cell proliferation and remodeling in asthmatic mice by up-regulating miR-181a and suppressing PTEN

Several studies have shown that transforming growth factor β1 (TGF-β1) plays a crucial role in remodeling and proliferation of airway smooth muscle cells (ASMCs). However, its molecular mechanism needs to be further studied. TGF-β1 can up-regulate the level of miR-181a in multiple cells, while miR-181a is expressed in asthma. We asked whether TGF-β1 plays a role in asthma through regulation of miR-181a. For this purpose, ASMCs were stimulated with TGF-β1 and the expression level of miR-181a and extracellular matrix (ECM) protein were measured by quantitative real time polymerase chain reaction (qRT-PCR) and western blotting. The cell proliferation and migration ability of TGF-β1-induced ASMCs were detected by Cell Counting Kit-8 (CCK-8) and transwell method, respectively. Luciferase assay was used to verify whether PTEN is a direct target of miR-181a in ASMCs. miR-181a expression level was increased in TGF-β1-induced ASMCs and miR-181a could inhibit the cell proliferation, migration, and excessive secretion of ECM. The results of the luciferase assay showed that miR-181a plays a role in TGF-β1-induced ASMCs targeting PTEN and the results of western blotting indicated that TGF-β1 could activate Akt/mTOR signaling pathway by up-regulating miR-181a and down-regulating siPTEN. In conclusion, TGF-β1 may induce airway smooth muscle cell proliferation and airway remodeling of asthma by up-regulating miR-181a and suppressing PTEN, and miR-181a inhibitor may function as an inhibitor of ASMCs proliferation through inactivation of the Akt/mTOR pathway.