Study On Hic-5 And TGF-β1/Smad Signaling Pathway In Scleroderma Fibrosis Pathogenesis Of The Skin

Objective:Scleroderma(SD) is a kind of chronic connective tissue disease with characteristics of fibrosis.Abnormal fibrosis channel,related protein expression and its regulation play an important role in the pathogenesis of fibrosis.In this experiment,we employed immunohistochemistry to investigate the expression of Hic-5, TGF-β1,Smad2/3 and Smad7 in scleroderma skin lesions,to explore the role of Hic-5 and TGF-β-mediated Smad transcription channel in the pathogenesis of fibrosis in scleroderma.Methods: Skin lesions from 40 patients with scleroderma patients was as SD group and 40 cases of normal skin tissue matched as control group. The SD group were confirmed by clinical and pathology examination.The expression of Hic-5,TGF-β1,Smad2/3 and Smad7 in 40 cases of SD group and 40 cases of control group were tested by immunehistochemical staining. All statistics were conducted by SPSS for windows Version17.0 with rank sum test,t test, χ2 test and Pearson correlation analysis,to analyze the possible relationships and significances of Hic-5,TGF-β1,Smad2/3,Smad7 in SD.Results:1.The expression of TGF-β1:In SD group,there were 27 cases positive expression out of 40 patients,the positive expression rate was 67.5%, among which 6 cases of(+),10 cases of(++),11 cases of(+++).The expression of TGF-β1 was mainly located in nucleus and cytoplasm of dermal fibroblasts. In the control group, 17 cases were weakly positive expression out of 40 cases, the positive expression rate was 42.5%.The experssion was mainly located in dermal fibroblasts cytoplasm. In the SD group compared with control group, the positive expression degree and positive expression rate of TGF-β1 in SD group were higher than the control group, the difference was statistically significant(P<0.05).2.The expression of Hic-5:There were 26 cases with positive expression of Hic-5 in SD group,the positive expression rate was 65.0%, among which 7 cases of(+),10 cases of(++),9 cases of(+++).The expression of Hic-5 was mainly located in nucleus and cytoplasm of dermal fibroblasts.In the control group,13 cases were weakly positive expression,the positiveex pression rate was 32.5%.The experssion was mainly located in dermal fibroblasts cytoplasm.In the SD group compared with control group,the positive expression degree and positive expression rate of Hic-5 in SD group were obviously higher than the control group,the difference was statistically significant(P<0.01).3.The expression of Smad2/3:There were 23 cases with positive expression of Smad2/3 in SD group,the positive expression rate was 57.5%, among which 5 cases of(+),11 cases of(++),7 cases of(+++).The expression of Smad2/3 was mainly located in nucleus of dermal fibroblasts. In the control group, 10 cases were weakly positive expression,the positive expression rate was 25.0%.The experssion was mainly located in cytoplasm of dermal fibroblasts. In the SD group compared with control group, the positive expression degree and positive expression rate of Smad2/3 in SD group were obviously higher than the control group, the difference was statistically significant(P<0.01). 4.The expression of Smad7: There were 22 cases with positive expression of Smad7 in SD group,the positive expression rate was 57.5%, among which 4 cases of(+),12 cases of(++),6 cases of(+++).The expression of Smad2/3 was mainly located in cytoplasm of dermal fibroblasts. In the control group, 12 cases were weakly positive expression,the positive expression rate was 35.0%.The experssion was mainly located in cytoplasm of dermal fibroblasts. In the SD group compared with control group, the positive expression degree and positive expression rate of Smad7 in SD group were higher than the control group,the difference was statistically significant(P<0.05).5.In SD group,the positive expression degree of TGF-β1 between Hic-5,Smad2/3,Smad7 were not statistically significant, comparable(W=1573, 1516, 1496,P>0.05).6.In SD group,the positive expression rate of TGF-β1 has positive correlations with Hic-5, Smad2/3 and Smad7(r=0.61,0.483,0.587, P<0.05).Conclusions:1.The positive expression of Hic-5 in SD group was obviously higher than the normal control group,Hic-5 may be involved in the pathogenesis of scleroderma skin fibrosis.2.The positive expression of TGF-β1,Smad2/3 and Smad7 in SD group was obviously higher than the normal control group,which implies abnormal activation of TGF-β1-mediated Smad signaling transcription pathway may be involved in scleroderma.3.The positive expression rate of TGF-β1 has positive correlations with Hic-5, Smad2/3 and Smad7,which implies that there may be interactions between the high expression of Hic-5 and the abnormal activation of TGF-β1/Smad signaling pathway in scleroderma.They may have a synergistic effect in the pathogenesis of scleroderma skin fibrosis.