Preliminary Study Of The Role Of LncRNA H19 In Asthma And Its Mechanism

Background: Asthma is a kind of heterogeneously allergic desease,classically characterized by eosinophilic airway high responsiveness(AHR),inflammation infiltration and mucin over-production.Recently,LncRNA was largely investigated in multiple diseases and played important regulatory roles by numerous mechanisms,while there were few reports concering to the role of LncRNA in asthma.Thus,revelation of the role of LncRNA in asthma might be helpful for furtherly understanding the pathology of asthma and improving treatments of asthma from the perspective of LncRNA.Objective: To investigate expression and roles of LncRNA H19 in asthma and its mechanisms.Methods: First of all,we detected expression of LncRNA H19 and Muc5 ac mRNA in asthma by establishing a murine asthma model via ovalbumin administeration.In vitro experiments,expression of LncRNA H19 and muc5 ac mRNA was also detected by treating bronchial epithelial cells 16-HBE with tumor necrosis factor(TNF-?)for 24 hours.Moreover,regulatory roles of LncRNA H19 in asthma were furtherly explored by overexpression or knock down via transfection of plasmids or siRNAs specific for LncRNA H19 in vitro experiments,respectively.To study regulatory effects of miR-675-3p on Muc5 ac,miR-675-3p mimics and inhibitors were respectively transfected into 16-HBE cells.To detect regulatory mechanisms of H19,16-HBE was treated with inhibitors of PI3 K.Expression of transcription factor p-NF-?B and p-Akt was determined by Western Blotting.Results: In line with reports of airways of asthmatics,LncRNA H19 was decreased,while muc5 Ac mRNA was increased in lung tissues of murine asthma model and 16-HBE cells treated with TNF-? in vitro.However,muc5 ac mRNA expression was increased or decreased by overexpression or knock down of LncRNA H19,respectively.Moreover,H19 overexpression furtherly increased TNF?-induced Muc5 ac expression,and H19 knockdown decreased TNF?-induced Muc5 ac expression.Western Blotting results showed that p-Akt and p-NF-?B was decreased by knock down of LncRNA H19.Inhibitors of PI3 K abolished increases of Muc5 ac induced by overexpression of H19.MiR-675-3p had no regulatory effects on Muc5 ac expression.Conclusions: LncRNA H19 positively regulated Muc5 ac mRNA expression via PI3K/Akt/ NF-?B pathway in vitro experiments.However,decreased LncRNA H19 and increased Muc5 ac mRNA were detected in asthma group compared with healthy controls,and in TNF? group compared with control group in vitro experiments.In view of that asthma is a complicated desease regulated by numerous factors,many mehanisms are involved in regulation of Muc5 ac expression in addition to H19.Among many mechanisms,decreased H19 might be a mechanism partly relieving mucin overproduction.