Effect Of Channel Protein TRPV4 On Matrix Deposition In Mucosal Remodeling Of Chronic Rhinosinusitis Without Polyps

Objective:By detecting the expression of transient receptor potential vanilloid 4(TRPV4)and transforming growth factor β1(TGF-β1)in patients with chronic rhinosinusitis without nasal polyps(CRSs NP),In vitro culture of primary cells,lipopolysaccharide(LPS)was used to stimulate nasal epithelial cells,and the expression of factors related to matrix deposition in mucosal remodeling: TGF-β1,MMP-9,MMP-2,TIMP-1 expression was observed.The situation was to investigate the effect of TRPV4 on matrix deposition in CRS mucosal remodeling.Methods:1.The protein expression levels and expression sites of TRPV4 and TGF-β1 in CRSs NP and normal controls were semi-quantitatively determined by immunohistoc-hemistry.2.The m RNA expression levels of TRPV4 and TGF-β1 in CRSs NP and normal control group were detected by real-time PCR(q RT-PCR)and correlation analysis was performed.3.Primary nasal mucosal epithelial cells were treated with different concentratio-ns(0,20,40,60,80,100 ng/m L)and LPS at different times(0,12,24,36,48 h)and detected expression of TRPV4 by q RT-PCR4.The cytokine TGF-β1 was added to the culture medium to induce the epithelial cells of the nasal mucosa,and a blank control was set.After 24 hours,the expression of mucosal remodeling factors MMP-9,MMP-2 and TIMP-1 m RNA were measured.5.LPS was applied to the epithelial cells of the nasal mucosa at the optimal concentration and stimulation time.The nasal mucosa epithelial cells were treated with TRPV4 specific blocker GSK2193874,and the matrix deposition related factors(TGF-β1,MMP-9,MMP-2,TIMP-1)in mucosal remodeling were detected by q RTPCR,The expression of TGF-β1 was detected by cellular immunofluorescence.Results:1.The results of immunohistochemistry indicated that TRPV4 and TGF-β1 were expressed in normal control group and CRSs NP.The protein expression levels of TRPV4 and TGF-β1 in CRSs NP patients were higher than those in normal control group.2.The q RT-PCR results of the specimen tissue experiments indicated that the expression of TRPV4 and TGF-β1 in CRSs NP patients was significantly higher than that in the normal control group,and the expression of the two factors was linearly positively correlated.3.The results of q RT-PCR in cultured nasal mucosal epithelial cells showed that the expression of TRPV4 m RNA increased with the increase of LPS stimulation concentration and stimulation time.4.After stimulation of nasal epithelial cells with cytokine TGF-β1,m RNA expression of MMP-9,MMP-2 and TIMP-1 was increased.5.LPS was applied to the epithelial cells of the nasal mucosa at the optimal concentration and stimulation time.The nasal mucosa epithelial cells were treated with TRPV4 specific blocker GSK2193874,and the expression of matrix deposition related factors in mucosal remodeling was detected by q RT-PCR.RESULTS:Compared with the DMSO control group,the expression of TGF-β1,MMP-9 and TIMP-1 was significantly decreased in the TRPV4 inhibitor group,and there was no significant difference in the expression of MMP-2.The results of cellular immunofluorescence showed that the expression of TGF-β1 protein was decreased compared with the DMSO control group.Conclusion:In CRSs NP,TRPV4 is closely related to TGF-β1,which regulates the deposition of matrix in CRSs NP mucosal remodeling by regulating the expression of TGF-β1.