Expressions Of β-catenin、dickkopf-2 And Glycogen Synthase Kinase-3β Of Wnt/β-catenin Signaling Pathway In Pulmonary Fibrosis

Objective:To observe the protein expression and significance of human Beta-catenin(β-catenin), Dickkopf(DKK)-2 and Glycogen synthase kinase-3beta(GSK-3β) of Wnt/β-catenin signaling pathway in lung fibrosis tissues, furthermore, analyze their association with fibrosis degree, and investigate the role of Wnt/β-catenin signaling pathway network factors in the development of pulmonary fibrosis.Methods:En Vision TM were performed to detect the expressions of β-catenin, DKK-2 and GSK-3β proteins in 23 patients of different severity of pulmonary fibrosis tissues and10 cases of normal lung tissue, the staining-grade was quantitatively analyzed by Integrated Optical Density(IOD) using Image Pro Plus 6.0 image analyzer. The relationship between the immunohistochemcal staining of these proteins and fibrosis degree were statistically evaluated by means of SPSS19.0 software package.Results:1. IHC positive rate of β-catenin expression in normal lung tissues and lung fibrosis were 30.0%(6/20), 84.6%(22/26), IOD value were 3213.30±838.43,42685.39±23775.89; positive staining in pulmonary fibrosis were significantly higher than that in normal lung tissue, compared in pairs, there are significant differences(P<0.05). The positive rate of β-catenin protein expression in mild(stage1),moderate(stage2) and severe(stage3) fibrosis group were 85.7.0%、81.8% and 87.5%,there were significant differences of positive rate in control, pulmonary fibrosis S1,S2, S3(P<0.05); IOD value were 17907.24±7988.30, 35861.73±7267.64 and73748.79±9941.97.16 respectively, statistical differences were significant between S1,S2, S3 and control group(P<0.05). The expression of β-catenin protein was significantly correlated to the fibrosis degree(rs=0.628, p<0.05).2. IHC positive rate of DKK-2 in normal lung tissue and lung fibrosis were35.0%(7/20), 76.9%(20/26), IOD value were 3213.30±838.43, 42685.39±23775.89;positive staining in pulmonary fibrosis were significantly higher than that in normal lung tissue, compared in pairs, there are significant differences(P<0.05). The positive rate of DKK-2 protein expression in mild(stage1), moderate(stage2) and severe(stage3) fibrosis group were 71.4%、81.5% and 87.5%, respectively, there was no statistically significant difference between the S1 and S0(P>0.05), there were significant differences of positive rate in control, pulmonary fibrosis S2, S3(P<0.05)(P<0.05); IOD value were 13073.31±3027.98, 35705.24±3974.76, 80599.72±9644.53,statistical differences were significant between the S1, S2, S3 and control group(P<0.05). The expression of DKK-2 protein was significantly correlated to the fibrosis degree(rs=0.529, p<0.05).3. IHC positive rate of GSK-3β expressed in normal lung tissue and lung fibrosis were 40.0%(8/20), 80.8%(21/26), IOD value were 2873.66±1911.36,41020.58±13419.85; positive staining in pulmonary fibrosis were significantly higher than that in normal lung tissue, compared in pairs, there are significant differences(P<0.05). The positive rate of GSK-3β protein expression in mild(stage1),moderate(stage2) and severe(stage3) fibrosis group were 71.4%, 72.7% and 100.0%respectively, there was no statistically significant difference between the S1,S2 and S0 group(P>0.05), there were significant differences of positive rates between the S0 and S3(P<0.05); IOD value were 31848.84±3739.34, 33926.60±4755.41,58829.77±8551.73 respectively, statistical differences were significant between S1,S2, S3 and control group(P<0.05). The expression of GSK-3β protein was significantly correlated to the fibrosis degree(rs=0.433, p<0.05).4. The intensitivities of β-catenin were showed to be positively correlated to that of DKK-2 protein(r=0.953, rs=0.619, p<0.05); β-catenin were showed to be positively correlated to that of GSK-3β protein(r=0.932, rs=0.456,p<0.05); β-catenin were showed to be positively correlated to that of GSK-3β protein(r=0.918, rs=0.498,p<0.05).Conclusion:1. β-catenin, DKK-2 and GSK-3β protein expression level in pulmonary fibrosisis significantly higher than normal lung tissue, furthermore the overexpression ofβ-catenin, DKK-2 and GSK-3β protein is positive correlation with fibrosis degree in human pulmonary fibrosis.2. The intensities of β-catenin DKK-2 and GSK-3β were showed to be positively correlated to each other, and it indicated that there existed interaction between the three proteins.3. Wnt/β-catenin signaling pathway activation may play an important role in the process of pulmonary fibrosis.