TNFSF14, a novel target of miR‐326, facilitates airway remodeling in airway smooth muscle cells via inducing extracellular matrix protein deposition and proliferation

As a common chronic respiratory disease, the incidence of asthma is increasing in recent years worldwide. Airway remodeling is the primary pathological basis of refractory asthma, but the studies about the underlying mechanism of airway remodeling was a lack. In the study, we aimed to investigate the effects and mechanisms of miR-326 on airway remodeling in airway smooth muscle cells (ASMCs). The results showed that transforming growth factor-beta1 (TGF-beta1) accelerated matrix protein deposition by increasing the expression levels of collagen I and fibronectin, and promoted proliferative ability of ASMCs. However, miR-326 was significantly downregulated in TGF-beta1-treated ASMCs. MiR-326 mimics robustly decreased the collagen I and fibronectin levels and inhibited cell proliferation of TGF-beta1-treated ASMCs. Luciferase assay investigated that tumor necrosis factor superfamily member 14 (TNFSF14) was a direct target of miR-326. The expression of TNFSF14 was negatively regulated by miR-326. Moreover, exogenous TNFSF14 effectively reversed the inhibitory effects of miR-326 overexpression on the expression levels of collagen I and fibronectin, and promoted cell proliferation of TGF-beta1-treated ASMCs. In conclusion, miR-326 suppressed matrix protein deposition and cell proliferation of TGF-beta1-treated ASMCs via inhibiting TNFSF14. MiR-326 might be a promising novel therapeutic target for asthma.