Full-Length Transcriptome Sequencing Analysis of Differentially Expressed Genes and Pathways After Treatment of Psoriasis With Oxymatrine

Abstract

Psoriasis is a recurrent chronic inflammatory skin disease. Unlike many of the latest psoriasis treatments that only confer limited curative effects and have certain side effects, oxymatrine effectively improves severe plaque psoriasis with mild adverse reactions. Here, we explored the genes and pathways underlying the effects of oxymatrine on psoriasis. Briefly, patients with severe plaque psoriasis were treated with oxymatrine and their lesioned skin samples were sequenced by full-length transcriptomics. Next, the differentially expressed genes (DEGs) in psoriatic lesions were identified and compared in oxymatrine-treated patients and healthy controls, their genes were functionally annotated, and protein–protein interaction network analysis and immunohistochemistry were performed. Both Psoriasis Area and Severity Index (PASI) and Body Surface Area (BSA) scores were recovered significantly from all 16 patients (all p < 0.001). The number of DEGs in patients before and after oxymatrine treatment was 4232, and 4105 DEGs were found between the psoriasis group (before oxymatrine treatment) and the normal control group [p < 0.01, |log2 fold change, (FC)| >1.5]. While most of the DEGs recovered significantly after oxymatrine treatment, only 650 DEGs were observed between the psoriasis group (after oxymatrine treatment) and the normal control group (p < 0.01, |log2FC|> 1.5). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that 64 pathways were significantly activated after oxymatrine treatment (p < 0.05). Only 12 pathways were statistically significant between after oxymatrine treatment and the normal control group (p < 0 .05). Among all the restored pathways, the improvement of the IL-17 signaling pathway was the most significant (p = 1.18E-06). Gene loci of oxymatrine action was assessed by protein interaction analysis on 205 DEGs that were co-expressed in 5 patients before and after oxymatrine treatment (p < 0.05, FC > 1.5). After oxymatrine treatment, the expression of two mitosis-related genes namely, cyclin dependent kinase 1 (CDK1) and cyclin B1 (CCNB1), that affect cell proliferation recovered significantly. In light of these results, we conclude that oxymatrine likely alters the abnormal expression of some genes and pathways in psoriasis patients. Multipathway and multitarget therapy can greatly ameliorate abnormalities in genes and pathways and effectively treat psoriasis. Importantly, among the DEGs, the proliferation-related genes, such as CDK1 and CCNB1, are likely important targets for treating psoriasis by oxymatrine. We believe that these findings may lead to a new treatment strategy for psoriasis.

Weighted Gene Co-Expression Network Analysis of Oxymatrine in Psoriasis Treatment

“…Further details can be found in our previous report. 22 Previously, we analyzed the differentially expressed genes from our transcriptome data and concluded that oxymatrine-mediated treatment of psoriasis involves multiple genes and pathways. In this study, we combined the changes in clinical PASI scores of patients with psoriasis before and after oxymatrine treatment with the WGCNA.…”

“…The inclusion criteria, exclusion criteria, criteria for withdrawal from the trial, oxymatrine treatment, and acquisition of normal skin were according to a previous report. 22 This research was approved by the Ethics Committee of the General Hospital of Ningxia Medical University (clinical trial registration number: CHICCTR-TRC-14004301, China). All patients signed an informed consent form, and all procedures involving human participants were conducted following the tenets of Helsinki Declaration.…”

“…21 In our previous study, we utilized transcriptomic analysis to identify differentially expressed genes before and after oxymatrine treatment and identified potential targets for the treatment of psoriasis. 22 Hence, in the current study, we aimed to characterize the target genes and regulated pathways of oxymatrine in the treatment of psoriasis. To this end, weighted gene co-expression network analysis (WGCNA) was used to construct a network of complex genes and pathways that may be affected by oxymatrine during the treatment period.…”

Identification of key genes and Construction of miRNA-mRNA regulatory network in Psoriasis based on Bioinformatics Analysis

“…The expression level of CCNB1 is low in the nucleus and cytoplasm in healthy skin, and is mainly expressed in the basal cell layer of the epidermis and some of the hair follicle infundibulum. The expression of CCNB1 in psoriatic lesions and all layers of the epidermis was signi cantly higher than that in healthy skin [15] . Related studies have shown that the cell cycle of patients with psoriasis is signi cantly shortened, and the high expression of CDK1 and CCNB1 promotes the proliferation of keratinocytes in psoriasis [16] .…”

“…Meanwhile, studies have shown that Wilms tumor 1-binding protein promotes keratinocyte proliferation by regulating CCNA2 and CDK2, promoting the development of psoriasis [14] . In the skin lesions of psoriasis patients, the expression of CDK1 was widely distributed in all layers of the epidermis [15] . The expression level of CCNB1 is low in the nucleus and cytoplasm in healthy skin, and is mainly expressed in the basal cell layer of the epidermis and some of the hair follicle infundibulum.…”