The Discussion Of GSK-3? And TGF-?1/Smad Signal Pathway In The Pathogenesis Of Chronic Rhinosinusitis With Nasal Polyps

Objective:Chronic Rhinosinusitis?CRS?is a chronic inflammatory disease of the nasal cavity and sinus mucosa,and CRS is a complex inflammatory disease.Chronic Rhinosinusitis is a umbrella term covering Chronic Rhinosinusitis without nasal polyps?CRSs NP?and Chronic Rhinosinusitis with nasal polyps?CRSw NP?.The situation we are facing in China is rapidly changing,an increasing rate of high incidence.but,we have not yet understood the pathogenesis and progression of CRSs NP and CRSw NP,which limits our diagnosis and treatment of the disease.The pathogenesis of chronic rhinosinusitis is still the emphasis and difficulty in department of otolaryngology.TGF-?1/Smad signal pathway is well studied and is clear associated with CRS and NP.Transforming growth factor-?1 superfamily signaling plays a critical role in the regulation of immune cell behaviour,Inflammatory cytokines release process and formation of extracellular matrix?ECM?.In general,signaling is initiated with ligand-induced oligomerization of serine/threonine receptor kinases and phosphorylation of the cytoplasmic signaling molecules Smad2 and Smad3 for the TGF-?1 pathway.Carboxy-terminal phosphorylation of Smads by activated receptors results in their partnering with the common signaling transducer Smad4,and translocation to the nucleus.Activated Smads regulate diverse biological effects by partnering with transcription factors resulting in cell-state specific modulation of transcription.Glycogen synthase kinase-3? is widely expressed in eukaryotes,This research is study the expression of GSK-3? and TGF-?1/Smad signal pathway discussion,try to find out the relationship between GSK-3? and Smad4 or GSK-3? and CTGF.The discussion of GSK-3? and TGF-?1/Smad signal pathway in the pathogenesis of chronic rhinosinusitis with nasal polyps maybe guide clinical drug use.Methods:1 We choose cases,and divided into two groups: NP group and control group.We choose cases in NP group according to EPOS 2012,sampes are nasal polyps in NP group and inferior turbinate mucosa in control group.All patients were from July 2015-January 2016 in the second hospital of Hebei medical university,department of otolaryngology.All patients were in need of endoscopic sinus surgery.13 Polyp tissues of NP were obtained from the patients who were subjected to nasal polypeetomy in our department.Inferior turbinate mucosa as control group were from 6 patients with septal deviation or patients with cerebrospinal rhinorrhea repaired under endoscope.All patients are 18-60 years old.All patients had not the history of asthma,allergy and not receiving steroids before four weeks.2 All samples of divided into two parts.Part 1 were dipped in 4% paraformaldehyde fixation,samples of part 1 routinely embedded in the paraffin,then,tissue sections of part 1 stained with HE and immunohistochemistry.Part 2 were throwed into liquid nitrogen,and transferred to the refrigerator at-80 degree or keepped in liquid nitrogen for real-time PCR.3 Tissue sections of HE,observe the inflammatory cells and capillary density.4 Tissue sections of immunohistochemistry,under optical microscope?Magnification,400×?select 5 random views to analyze the expression of CTGF,Smad4,and GSK-3?.Using Image-pro-plus system to obtain optical density?OD?and analyze the expression of CTGF,Smad4,and GSK-3?.5 Samples of part 2 tested by real-time PCR to analyze the expression of CTGF,Smad4,and GSK-3?.Using Light Cycler Data Analysis to obtain the Ct value and the formula of RQ=2-??Ct.RQ indicates the gene expression of CTGF,Smad4,and GSK-3?.All data were analyzed by SPSS21.0.Results:1 There were no significant differences in age,gender between NP group and control group.2 Tissue sections of HE.In NP group,nasal polyps are full of intense inflammatory cell and with high capillary density,in control group inferior turbinate mucosa are with less inflammatory cell and capillary.3 Tissue sections of immunohistochemistry.Cells with brown granules are positive staining.In NP group,dark brown granules are much more than control group.The expression of CTGF,Smad4,and GSK-3? were significantly increased in NP group than control group(t_CTGF=3.51,P<0.01;t_Smad4=2.22,P=0.04;t_GSK-3?=4.95,P<0.01,?=0.05).4 The results of RT-PCR are same with IHC,the mRNA of CTGF,Smad4,and GSK-3? was increased in NP group than control group(t_CTGF=5.80,P<0.01;t_Smad4=2.83,P=0.01;t_GSK-3?=2.80,P<0.01,?=0.05).Conclusions:1 nasal polyps are full of intense inflammatory cell and with high capillary density.2 The expression of CTGF,Smad4,and GSK-3? were significantly increased in NP group than control group.3 CTGF,Smad4,and GSK-3? may play an important role in the pathogenesis of NP.