TNFSF11/TNFRSF11A Axis Amplifies HDM-Induced Airway Remodeling by Strengthening TGFβ1/STAT3 Action
Dong Zhang, Jintao Zhang, Qian Qi, Yun Pan, Rong Zeng, Changjuan Xu, Xiaofei Liu, Jiawei Xu, Mingxia Gao, Tingting Gao, Jian Zhang, Shuochuan Shi, Liang Dong
Abstract
PURPOSE: Asthma, an airway inflammatory disease, involves multiple tumor necrosis factors (TNF). TNF ligand superfamily member 11 (TNFSF11) and its known receptor, TNF receptor superfamily 11A (TNFRSF11A), has been implicated in asthma; however, the related mechanisms remain unknown. METHODS: ) using lentivirus to further examine the ability of TNFSF11 protein. RESULTS: shRNA in HBE cells. The above results also verified that blocking TNFSF11 with denosumab alleviated airway remodeling via the TGFβ1/STAT3 signaling in the humanized HSC-NOG-EXL mice with HDM-induced asthma. CONCLUSIONS: TGFβ1/STAT3 action was closely correlated with TNFSF11/TNFRSF11A axis-mediated airway remodeling. This study presented a novel strategy that blocks the TNFSF11/TNFRSF11A axis to exert a protective effect against asthma.