AbstractBackgroundChronic obstructive pulmonary disease (COPD) is one of the diseases with high mortality and morbidity with complex pathogenesis. Airway remodeling is an unavoidable pathological characteristic. However, the molecular mechanisms of airway remodeling are incompletely defined.MethodslncRNAs highly correlated with transforming growth factor beta 1(TGF–β1) expression were chosen, the lncRNAENST00000440406(named HSP90AB1 Assoicated LncRNA 1,HSALR1) was chosen for further functional experiments. Dual luciferase and ChIP assay were used to detect the upstream of HSALR1, transcriptome sequencing, Cck–8, Edu, cell proliferation, cell cycle assay, and WB detection of pathway levels confirmed the effect of HSALR1 on fibroblast proliferation and phosphorylation levels of related pathways. Mice was infected with adeno–associated virus (AAV) to expressHSALR1by intratracheal instillation under anesthesia and was exposure to cigarette smoke, then mouse lung function was performed and the pathological sections of lung tissues were analyzed.ResultsHerein, lncRNAHSALR1was identified as highly correlated with the TGF–β1 and mainly expressed in human lung fibroblasts. HSALR1 was induced by Smad3 and promoted fibroblasts proliferation. Mechanistically, it could directly bind to HSP90AB1 protein, and acted as a scaffold to stabilize the binding between Akt and HSP90AB1 to promote Akt phosphorylation. In vivo, mice expressedHSALR1by AAV was exposure to cigarette smoke (CS) for COPD modeling. We found that lung function was worse and airway remodeling was more pronounced in HSLAR1 mice compare to wild type (WT) mice.ConclusionOur results suggest that lncRNAHSALR1binds to HSP90AB1 and Akt complex component, and enhances activity of the TGF–β1 smad3–independent pathway. This finding described here suggest that lncRNA can participate in COPD development, andHSLAR1is a promising molecular target of COPD therapy.