| Background:Psoriasis is a chronic inflammatory skin disease prone to recurrent attacks.It typically presents with infiltrative erythema,papules,or silvery white scales.Its histopathology is characterized by hyperkeratosis,incomplete Keratosis,hypertrophy of the spine,proliferation and expansion of the Dermal Papilla,and infiltration of inflammatory cells in the superficial layer of the epidermis.According to ancient clssics of Chinese medicine,names of this disease include "Baibi","white shell sore","psoriasis","wind tinea","Pine Skin Pipi","snake Louse"and "yinxiebing".In recent years,the prevalence of psoriasis has been found to increase year by year.The total number of psoriasis cases in China is estimated to be between 6 million and 7 million in 2018.Psoriasis involves joint damage,diabetes,cardiovascular disease,obesity and other complications according to degrees of involvement,especially among young adults.It affects the physical and mental health of patients,and thus deteriorates the quality of life.Therefore,psoriasis is one of the most serious dermotological diseases.However,the etiology of psoriasis is complex and the pathogenesis is still uncertain.A large number of studies have shown that this disease as a complex disease is under a multi-factor genetic model,which can be caused by heredity,immunity,infection and a variety of environment.Many genes and signal pathways have been found to play an important role in the initiation and progression of psoriasis,including Th17/IL-17,JAK-STAT and PPAR signal pathways.With the gradual development of related research,although we have had a lot of new knowledge and research results on psoriasis,an inflammatory skin disease with strong heterogeneity,which is related to genetic and immune disorders,there is still a lack of biomedical data mining,collection and collation,and the molecular mechanism of psoriasis is still unknown so far.There are many problems lurking among the specific factors related to the disease,and these tight networks have not been tapped;therefore the targeted therapeutic drugs for clinical use cannot be invented.In recent years,compared with a large number of data processing,high-flow data analysis and information screening have become an important means of research,providing a new platform for traditional medical biology research.The present study aims to explore the molecular mechanism of psoriasis vulgaris by integrating information from the current bioinformatics database to identify the key genes for psoriasis vulgaris,and to provide theoretical basis and basis for further study of the disease.Chinese medicine has a lot of effective therapies of psoriasis.Mudanpi(Moutan Cortex),one of the most frequently used antipyretic herbs for psoriasis blood fever,is recorded in Shennong's Classic of Material Medica.Many researchers have found that Paeonol,as the main active component of CORTEX Moutan,is closely related to the pathogenesis of psoriasis since it has anti-inflammatory,neuroprotective,vascular protective,anti-proliferation and anti-oxidation effects.However,a lack of systematic and rigorous research on the molecular level of Chinese medicine in the treatment of psoriasis,and the specific mechanism of effective monomer in Chinese medicinals in the treatment of psoriasis has not been explored.Therefore,it is of great significance to increase the study of the etiology and pathogenesis of Psoriasis and the therapeutic principles and methods of TCM,especially to further explore the target and mechanism of the action of TCM monomer in the treatment of psoriasis,so as to broaden our thinking and obtain more satisfactory clinical curative effect.Objective:To screen psoriasis gene by bioinformatics,to further explore the pathogenesis of psoriasis,and to screen the target gene of Paeonol for psoriasis.Based on the identification of the key genes,the effects of Paeonol and ATG5 on the proliferation of Hacat cells and the expression of related factors were studied by cell experiments.In order to further use of Chinese medicine monomer treatment of psoriasis to provide the basis for the search for treatment targets,and to obtain satisfactory clinical treatment results.Research methods:This paper is divided into three parts,including an overview of the progress of Chinese medicine and Western medicine for psoriasis,as well as bioinformatics analysis and cell experiments.1.Progress of psoriasis in Chinese medicine and Western medicine.2.Bioinformatics.In this part,expression profiling data screening and Data pre-processing,Meta analysis were performed to screen consistently significant differential expressed genes,WGCNA algorithm was used to screen disease related significantly stable gene modules,and gene product protein interaction network was constructed,finally,psoriasis-related genes and paeonol-targeted genes were screened out.3.Cell Experimental Study:to investigate the effects of Paeonol and ATG5 on the proliferation,apoptosis and expression of related factors in HaCaT cells.The expression of ATG5,IL-1 and IL-6 were detected by ELISA,the expression of ATG5,IL-1 and IL-6 were detected by PCR,and the protein contents of Beclin 1,ATG5 and P62 were detected by Western blot.Result:1.A total of 779 DEGs were identified in lesion samples compared with non-lesion tissues.Autophagy-associated gene 5(ATG5)is the only gene that overlaps with genes associated with paeonol and psoriasis.2.Cell Experiment(1)Paeonol inhibits the proliferation of HaCaT cells induced by IL-22/TNF-and decreases the expression of IL-6,IL-1,Beclin 1,ATG5 and P62 in HaCaT cells.The effect of Paeonol on apoptosis was not obvious.Paeonol had no effect on the expression of IL-6,IL-1,Beclin 1,ATG5 and P62 in HaCaT cells transfected with si-ATG5 and pc-ATG5.(2)si-ATG5 could decrease the proliferation activity,accelerate the apoptosis,increase the expression of IL-6 and IL-1,decrease the expression of Beclin 1,ATG5 and P62,but the effect of pc-ATG5 was opposite.Conclusion:ATG5 gene plays an important role in the pathogenesis of psoriasis and may be the target of paeonol.The effect of paeonol on psoriasis cell model was ATG5-dependent,whose autophagy has been proved to be of great value in psoriasis.The content of ATG5 in the lesion tissue was higher than that in the non-lesion tissue.Inhibition of ATG5 can promote the inflammatory response of HaCaT cells induced by IL-22/TNF-,whereas overexpression of ATG5 can inhibit the inflammatory response of HaCaT cells.The inhibition of ATG5 may be a targeted therapeutic strategy for psoriasis.However,more experiments are needed to confirm the association between autophagy and psoriasis and the possibility of targeted autophagy therapy for psoriasis. |
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