Font Size: a A A

Expression Of C/EBP? In Psoriasis Vulgaris Lesions And Its Effect On IL-6/STAT3 Signaling Pathway

Posted on:2019-11-14Degree:MasterType:Thesis
Country:ChinaCandidate:L D LiuFull Text:PDF
GTID:2404330545461412Subject:Dermatology and Venereology
Abstract/Summary:PDF Full Text Request
Background and objective: Psoriasis is a polygene involved erythematosus scaly skin disease,which is a kind of chronic inflammatory disease with genetic predisposition.It's immune-mediated and has been a hot area of skin disease research for a long time.Studies have shown that Transcription factor CCAAT enhancer binding protein(C / EBP?)and STAT3 are activated after being stimulated by IL-6,and then transfer from the cell surface to nucleus,involving in gene transcription.C / EBP? is phosphorylated and activated by Rasdependent MAP kinase cascade after being stimulated by IL-6,while STAT3 is directly phosphorylated by JAK kinase tyrosine which is partial related to the cytoplasm of the receptor,then completes the translocation to nucleus and activates transcription(JAKSTAT pathway)[1].C / EBP? is highly expressed in epidermis of mouse and human and plays an important role in maintaining the orderly differentiation of keratinocytes [2-4].However,the expression of C/EBP? in abnormal hyperplastic and differentiated lesions and keratinocytes with psoriasis is little reported.The purpose of this research is to study the expression and distribution of C/EBP? in skin lesions of patients with psoriasis vulgaris,to determine whether C/EBP beta is involved in the formation of psoriatic lesions;2.To study on the correlation between C/EBP beta protein and psoriasis area-and severity index(PASI)in psoriatic lesions,to clarify the relationship between C/ EBP beta and the severity of psoriasis;3.To study on the correlation between the differential expression of C/EBP,STAT3 and p STAT3 in skin lesions,to explore whether C/EBP beta affects the IL-6/STAT3 signaling pathway.Methods:1.Participants: 15 cases with psoriasis vulgaris were patients from dermatology outpatients in our hospital from December 2016 to May 2017,and 10 normal people were the patients who had done orthopedic surgery in our hospital,to collect psoriasis patients' skin lesions(experimental group)and normal human skin tissue(control group).2.To investigate the involvement of C/EBP? in the formation of psoriatic lesions: the expression and distribution of C/EBP?,STAT3 and p STAT3 protein were detected by immunohistochemical staining in experimental and control groups respectively;Western blot,PT-PCR are used to test expression of C/EBP? protein and m RNA in two groups and to analyze their differential expression.3.Correlation between C/EBP? and the severity of psoriasis: To test C/EBP? protein expressed in the lesions of experimental group by Western blot,and to analyze the correlation between the psoriasis area and PASI score.4.To investigate whether C/EBP? affects the expression of IL-6/STAT3 signaling pathway: The expression of C/EBP? and p STAT3 protein in psoriatic lesions were detected by Western blot,and correlations between the expression of C/EBP? and p STAT3 protein were analyzed.Results: 1.Clinical data: 15 patients with psoriasis vulgaris,9 were males and 6 were females,aged from 17 to 54(average age,35.867 ± 12.949 years).Course was from 3 months to 10 years(average course,6.75 ± 6.28 years).PASI score were from 2.4 to 18.8.10 cases of normal control group,5 males and 5 females;aged 20 to 40(average age,26.70 ± 6.583).There are no statistical differences between the patients with psoriasis vulgaris and normal controls in sex(X2 = 0.244,P> 0.05)and age composition(P> 0.05).2.Immunohistochemical results: The normal controls,C/EBP? is abundantly expressed in the nucleus of each layer of epidermal cells,while in experimental groups,the expression of C/EBP? is significantly reduced and it is mainly expressed in the superior part of stratum spinosum;And in experimental group,STAT3 and p STAT3 were widely distributed in the nucleus,perinuclear region and cytoplasm of each layer of epidermal cells,while the expression level of STAT3 and p STAT3 in the normal controls was obviously lower than those of experimental group.3.Western blot and PT-PCR results: The expression level of C/EBP? protein(0.843 ± 0.41)and m RNA(0.479 ± 0.307)in the skin lesions of patients with psoriasis was lower than that of normal control group,C/EBP? protein(1.15 ± 0.26)and m RNA(0.732 ± 0.126)(P < 0.05),and p STAT3 protein level(0.28 ± 0.065)was higher than that of normal control group(0.177 ± 0.034)(P < 0.05).4.Correlation analysis: The expression of C/EBP? protein in psoriasis patients was negatively correlated with PASI score(r =-0.661,P <0.05),and negatively correlated with the expression of p STAT3 protein(r =-0.629,P <0.05).Conclusion: 1.The expression of C/EBP ? in patients with psoriasis was significantly lower than that of normal tissue and was mainly expressed in the nucleus in stratum spinosum,which indicated that there was a certain relationship between C/EBP? and abnormal differentiation of the keratinocytes in psoriasis.2.The level of C /EBP? protein and m RNA in psoriasis was lower than the normal controls,and the level of C/ EBP? protein in the lesions was negatively correlated with PASI score,which indicated that C/EBP? might be involved in the abnormal proliferation of keratinocytes in psoriasis.3.The level of C/EBP? protein in psoriatic lesions was negatively correlated with PSTAT3,which indicated that C/EBP? might affect the IL-6/STAT3 signaling pathway,thus led to the pathogenesis of psoriasis.
Keywords/Search Tags:psoriasis vulgaris, C/EBP?, IL-6/STAT3
PDF Full Text Request
Related items