Mechanism Research On The Transcription Of Mouse ORMDL3 Gene Up-regulated By Recombinant Platanus Pollen Allergen2(rPla A2)

Objective:To explore the transcriptional mechanism of transcription factor GATA3 on mouse orosomucoid 1-like 3(ORMDL3)gene,and to identify the effect and mechanism of recombinant platanus pollen allergen 2(rPla a2)on the transcription and expression of ORMDL3 gene in NIH3T3 cells in aims of seeking new therapeutic target for the prevention and treatment of allergic asthma caused by inhalation allergen.Methods:CHIP was carried out to identified to identify the binding of transcription factor GATA3 to mouse ORMDL3 promoter.After transient transfection of GATA3 siRNA or pcDNA-GATA3,the effect of GATA3 on ORMDL3 expression was detected.Luciferase reporter assay,quantitative real-time PCR and Western blot analysis were used to detect the influence of rPla a2 on the mRNA and protein levels of ORMDL3 and GATA.Meanwhile,the DNA binding of GATA3 to ORMDL3 promoter was detected by ChIP-qPCR.Results:GATA3 could directly bind to the core promoter of mouse ORMDL3 promoter and up-regulate ORMDL3 expression,but failed to bind to-?-bp.ORMDL3 promoter activity was significantly promoted by rPla a2 and inhibited by knockdown of GATA3.rPla a2 increased ORMDL3 promoter activited mediated by GATA3 and STAT6.And rPla a2 induced mRNA and protein expressions of ORMDL3 and GATA3.Knockdown of GATA3 inhibited the induction of rPla a2 upon ORMDL3.In addition,the bingind between GATA3 and ORMDL3 promoter was enhanced by rPla a2.Conclusion:GATA3 positively regulated mouse ORMD3 gene which provides a theoretical basis for the treatment of asthma with GATA3 as target.rPla a2 up-regulates the transcription and expression of ORMDL3 mediated by GATA3 through enhanced binding to ORMDL3promoter.Our results provide new ideas for the treatment of allergic asthma induced by plant aeroallergen.