Study On The Regulation Of Epithelial Tight Junction In Allergic Rhinitis By Cystatin SN Through The JAK1/STAT6 Pathway

Objective:To investigate the effect of endogenous Cystatin SN(CST1)on the expression of tight junctions(TJs)in nasal mucosa epithelium of patients with Allergic rhinitis(AR).Methods:1.We detected CST1,TJs and pathway molecules in nasal mucosas from healthy control and AR patients,using IHC,RT-q PCR,and Western blot.We analyzed the correlation between CST1 and TJs,pathway molecules expression in AR.2.Nasal mucosal tissues were taken for human primary culture nasal mucosal epithelial cells,and AR model was induced with Der p1,a house dust mite allergen.AR model was stimulated with CST1 to detect the TJs and pathway molecules.3.AR cell models were treated with CST1 and STAT6 inhibitors alone or in combination,and detected the expressions of CST1,TJs and pathway molecules,respectively.Results:1.The expression of CST1,JAK1,JAK3,STAT6,and p-STAT6 in AR was significantly higher than control,but ZO-1,Claudin-1,-7,JAM-A,and Occludin in AR decreased significantly.Correlation analysis showed that CST1 was positively correlated with the expression of Claudin-1 and ZO-1,and negatively correlated with the expression of JAK1 and STAT6.2.In Der p1-induced AR model,18 h observation showed that the expression of CST1 decreased after 15 h to the peak,while the expression of TJs was decreased with the extension of time.In order to study the effect of CST1 on TJs,18 h with low CST1 expression was selected as the modeling time.stimulation of AR model by CST1 resulted the increased expression of ZO-1,Claudin-1,Claudin-7 and JAM-A,and decreased expression of total STAT6 and p-STAT6.3.The expression of Claudin-1 and JAM-A was increased and the expression of STAT6 and p-STAT6 was decreased in the AR model treated with STAT6 inhibitor.The expression of ZO-1 and Claudin-1 was significantly increased while the expression of STAT6 and p-STAT6 was significantly decreased in AR cells treated with CST1 and STAT6 inhibitors.Conclusion:The expression of CST1 in AR is elevated,and the damage of the TJs is blocked by the control of the JAK1/STAT6 signal pathway.It has a synergistic effect with STAT6 inhibitor and plays an important role in protecting nasal mucosal epithelium from allergen protease invasion.The application of endogenous protease inhibitors may have a therapeutic effect on AR.