| Chronic rhinosinusitis with nasal polyps is charactered as chronicinflammation of the nose and sinuses. The pathology is characterized by nasaland sinus mucosal edema, inflammatory changes. Nasal polyps isCharacterized by a high prevalence and recurrence rate, The overallprevalence of chronic rhinosinusitis was10.9%from EPOS2012. The effectivetreatments of functional endoscopic sinus surgery (FESS) and topicallyadministered glucocorticoids are not yet proven as the recurrence rate is about20%. Nasal polyps is a significant health problem which results in a largefinancial burden on society.Varieties factors contribute to nasal polyps are many, such as intrinsic upperairway factors, immune system defects,infections (including bacterial viral,and fungal), allergic rhinitis or muco-ciliary clearance impairment. Recentstudies have found that some endogenous or exogenous protein receptorbinding proteins may be immune cells recognize pathogen-associatedmolecular patterns by stimulating downstream signaling pathways promote thesecretion of inflammatory cytokines, which play an inflammatory reaction.The silent information regulator2(Sir2) family is composed of seven proteins,class III histone NAD+-dependent protein deacetylases, have been implicatedin cellular senescence, calorie restriction and signaling pathways upstream ofinflammation. It was recently reported that Sirt1and Sirt6were involved inCOPD pathogenesis through prevention of stress-induced inflammation andpremature cellular senescence. So we note the sirtuin family with regulatorymechanism for nasal polyps pathogenesis. This study will observe thedifferences of Sirt1and Sirt2protein expression between nasal polyps andnormal nasal mucosa tissue by immunohistochemical examination and westernblot; to evaluate the function of Sirt6in primary cultured human nasalepithelial cells in vitro, thus to provide a theoretical basis for furtherimproving its prevention and treatment. Part one:Expression of Sirt1and Sirt2in chronic rhinosinusitiswith nasal polypsObjectives: To investigate the expression of Sirt1and Sirt2in CRSwNPMethods: Thirty-eight patients with CRSwNP and eight control subjects wererecruited for immunohistochemical examination and Western blot, to observethe distribution and levels of Sirt1and Sirt2protein.Results:1. Sirt1positive staining distributed in the glandular cells of thenormal nasal mucosa and the inflammatory cells of nasal polyps, but Sirt1significantly decreased in glandular cells of nasal polyps. Sirt2positivestaining mainly distributed in the cytoplasm of epithelial cells. The expressionof Sirt2was increased in the control group compared with nasal polyps group2.Western blot showed that the levels of Sirt1and Sirt2protein in the controlgroup were significantly higher than nasal polyps group (P＜0.01).Conclusion: There is a certain amount of Sirt1and Sirt2expression in normalnasal mucosa, its reduced expression may be involved in the formation andinflammatory reactions associated with chronic sinusitis and nasal polyps.Part two:Effect of Sirt6in nasal epithelial cells with its gene knocked downObjectives: to investigate the effect of Sirt6on cilia differentiation andHMGB1expression in nasal epithelial cells with its gene knocked down.Methods: Primary cultured nasal polyp epithelial cells transfected with siRNASirt6by liposome transfection. β-tublin and Sirt6protein were assessed byWestern blot. The expression and distribution of HMGB1protein and ciliawere observed using immunfluorescence assay.Results: Sirt6was stably expressed in nasal epithelia cells. Compared withnon-transfected group, β-tublin and Sirt6was significantly decrease aftersiRNA Sirt6transfection using immunofluorescence assay and western blot.Sirt6knockdown induced HMGB1proteins to shift from the nucleus to thecytoplasm, as well as to change the morphology of epithelial cells. Conclusion: These results suggest that Sirt6is involved in nasal epithelialcilia differentiation and can be attributed to translocation of HMGB1protein. |
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