Experimental Study On The Effect Of SENP3 On Nasal Polyp Formation By Mediating Macrophage Alternative Activation In Chronic Sinusitis

Objective: This study aimed to explore how SENP3 influenced the outcome of chronic rhinosinusitis SENP3(SUMO-specific protease,SENP)by altering macrophage function,that is,the formation of NPs(Nasal Polyps).Methods:Clinical trials according to the score under endoscopy and CT in 41 cases with Chronic nasal sinusitis-(Chronic sinusitis,CRS)surgery patients,diagnosed with Chronic nasal sinusitis-nasal polyps(Chronic sinusitis with nasal polyps,CRSwNP)group(N = 28)and Chronic nasal sinusitis without polyps(Chronic sinusitis with nasal polyps,CRSs NP)group(N = 13)and do not overlap into groups,A total of15 cases(CRSwNP: CRSs NP=10:5)and 27 cases(CRSwNP: CRSs NP=18:8)were stained by immunofluorescence respectively for co-localization analysis of CD68+CD206+ and SENP3 expression,as well as quantitative analysis of CD68+CD206+ cells and CD68+CD80+ cells to determine the correlation between substitution activated macrophages(M2)and SENP3 expression in nasal mucosal inflammation and nasal polyps.In cell and animal experiments,8-week male SENP3 knockout(SENP3 cKO)and SENP3 flox/flox(SENP3 fl/fl)C57 BL/6 mice were used to establish the animal model system of primary bone marrow derived macrophages(BMDM)and allergic rhinitis.F4/80+CD206+ detection was performed on BMDM of SENP3 cKO after il-4& il-13(interleukin-4& interleukin-13)was added to induce replacement activation of macrophages(M2)to determine the effect of SENP3 knockout on macrophages polarization phenotype.Western blot was used to determine the role of SENP3 in macrophage replacement activation in wild-type mouse bone marrow derived macrophages induced by il-4 &IL13.For the animal model of allergic rhinitis constructed after 12 weeks of continuous nasal OVA(ovalbumin),immunofluorescence staining of paraffin sections was used to detect the number of CD206+ in macrophages SENP3 cKO and SENP3 fl/fl groups as well as eosinophil specific staining.Results: compared with patients with chronic rhinosinusitis without polyps,the number of CD68+ CD206+ M2 macrophages in nasal mucosa increased in patients with chronic rhinosinusitis without polyps.However,there was no significant difference in CD68+ CD80+ M1 macrophages.In an in vitro induced macrophage polarization model,knockout of SENP3 increased the polarization of f4/80 +CD206+M2macrophages.Meanwhile,in the allergic rhinitis model of SENP3 cKO group and SENP3 fl/fl group,CD206+M2 macrophages increased significantly,and eosinophil infiltration of nasal mucosal tissue hyperplasia was more obvious.Conclusion: in chronic sinusitis,the down-regulation of the expression of SENP3 in the nasal mucosa promotes the formation of nasal polyps.