The Expression And Function Of Hypoxia-inducible Factor In Nasal Polyps

Background and ObjectivesChronic rhinosinusitis(CRS)is a non-specific term that is used to describe any chronic inflammatory condition of the paranasal sinuses.Chronic rhinosinusitis with nasal polyps(CRSwNP)seems to be more likely to have a refractory clinical process.CRSwNP is characterized by edematous stroma,immune cell infiltration and epithelial thickening and denudation.Although hypoxia is believed to be associated with CRSwNP,little is known about the mechanism underlying polypogenesis.The response of cells to hypoxia is characterized by specific alterations in the expression of a large number of genes,many of which are regulated directly or indirectly by hypoxia-inducible factor(HIF).HIF is a transcriptional regulator that plays a key role in many aspects of oxygen homeostasis.The aim of this study was to evaluate the expression and function of HIF-la,HIF-2a,HIF-3a in CRSwNP,and to provide some suggestion for CRSwNP treatment.Methods40 nasal polyps and 20 normal inferior turbinate mucosa samples were obtained by endoscopic sinus surgery,according to the principal of informed consent.Fresh tissues were divided into two sections,one was fixed in 4%formalin and another was preserved in RNA later.Cell morphology observed by H&E staining,immunohistochemical staining and immunofluorescence staining,real-time quantitative PCR methods were used to compare mRNA expression levels between control group and nasal polyps group.All data were analyzed using SPSS statistical software.The Mann-Whiney two-tailed test was performed to compare protein/mRNA levels of selected genes between control group and nasal polyps group.Spearman's rank analysis was used to assess the correlation of selected genes.p<0.05 was considered significant.Results1.HIF-1? mRNA and protein expression have no significant difference between nasal polyps group and controls;HIF-2a mRNA expression is significantly lower in nasal polyps group than that of controls(p<0.01),HIF-2a staining immunoreactivity is significantly weaker in nasal polyps group than that of controls(p<0.01);HIF-3a mRNA expression is significantly lower in nasal polyps group than that of controls(p<0.01),HIF-3a protein expression has no significant difference between nasal polyps group and controls.2.HIF-la,HIF-2a and HIF-3a expressed in different tissue locations,HIF-la and HIF-3a mainly expressed in epithelia,while HIF-2a mainly expressed under epithelial,around both glands and vessels.3.VE-cadherin mRNA expression is significantly lower in nasal polyps group than that of controls(p<0.01),VE-cadherin staining immunoreactivity is significantly weaker in nasal polyps group than that of controls(p<0.01).The mRNA expression of HIF-2a has a significant positive correlation with VE-cadherin(p<0.01),the protein expression of HIF-2a and VE-cadherin shows some co-localizations around the blood vessels.ConclusionsDifferent expression patterns of HIF-la,HIF-2a and HIF-3? in nasal polyps imply that they may play different roles in pathogenesis.HIF-2a may be associated with the decreased expression of VE-cadherin in nasal polyps.HIF-a may become potential treatment targets for nasal polyps.