Identification of potential key molecules and signaling pathways for psoriasis based on weighted gene co-expression network analysis

BACKGROUND Psoriasis is a chronic inflammatory skin disease,the pathogenesis of which is more complicated and often requires long-term treatment.In particular,moderate to severe psoriasis usually requires systemic treatment.Psoriasis is also associated with many diseases,such as cardiometabolic diseases,malignant tumors,infections,and mood disorders.Psoriasis can appear at any age,and lead to a substantial burden for individuals and society.At present,psoriasis is still a treatable,but incurable,disease.Previous studies have found that micro RNAs(mi RNAs)play an important regulatory role in the progression of various diseases.Currently,mi RNAs studies in psoriasis and dermatology are relatively new.Therefore,the identification of key mi RNAs in psoriasis is helpful to elucidate the molecular mechanism of psoriasis.AIM To identify key molecular markers and signaling pathways to provide potential basis for the treatment and management of psoriasis.METHODS The mi RNA and m RNA data were obtained from the Gene Expression Omnibus database.Then,differentially expressed m RNAs(DEm RNAs)and differentially expressed mi RNAs(DEmi RNAs)were screened out by limma R package.Subsequently,DEm RNAs were analyzed for Gene Ontology and Kyoto Encyclopedia of Genes and Genomics functional enrichment.The“WGCNA”R package was used to analyze the co-expression network of all mi RNAs.In addition,we constructed mi RNA-m RNA regulatory networks based on identified hub mi RNAs.Finally,in vitro validation was performed.All experimental procedures were approved by the ethics committee of Chinese PLA General Hospital(S2021-012-01).RESULTS A total of 639 DEm RNAs and 84 DEmi RNAs were identified.DEm RNAs screening criteria were adjusted P(adj.P)value<0.01 and|log Fold Change|(|log FC|)>1.DEmi RNAs screening criteria were adj.P value<0.01 and|logFC|>1.5.KEGG functional analysis demonstrated that DEm RNAs were significantly enriched in immune-related biological functions,for example,tolllike receptor signaling pathway,cytokine-cytokine receptor interaction,and chemokine signaling pathway.In weighted gene co-expression network analysis,turquoise module was the hub module.Moreover,10 hub mi RNAs were identified.Among these 10 hub mi RNAs,only 8 hub mi RNAs predicted the corresponding target m RNAs.97 negatively regulated mi RNA-m RNA pairs were involved in the mi RNA-m RNA regulatory network,for example,hsa-mi R-21-5 pclaudin 8(CLDN8),hsa-mi R-30 a-3 p-interleukin-1 B(IL-1 B),and hsa-mi R-181 a-5 p/hsa-mi R-30 c-2-3 p-C-X-C motif chemokine ligand 9(CXCL9).Real-time polymerase chain reaction results showed that IL-1 B and CXCL9 were up-regulated and CLDN8 was down-regulated in psoriasis with statistically significant differences.CONCLUSION The identification of potential key molecular markers and signaling pathways provides potential research directions for further understanding the molecular mechanisms of psoriasis.This may also provide new research ideas for the prevention and treatment of psoriasis in the future.

Comprehensive transcriptome analysis based on RNA sequencing identifies critical genes for lipopolysaccharide-induced epididymitis in a rat model

Epididymitis is a comm only diagnosed disease associated with male infertility.However,little is known about the molecules that are involved in its development.This study was to identify critical genes associated with lipopolysaccharide-induced epididymitis and an a lyze the molecular mecha nism of epididymitis through RNA sequencing.Experime ntal epididymitis models were generated by administering male Sprague-Dawley rats'lipopolysaccharide.A total of 1378 differentially expressed genes,including 531 upregulated and 847 down regulated gen es,were identified in the epididymitis model rats compared with those in sham-operated rats by RNA seque ncing.Fun ctional enrichme nt an a lyses suggested that the upregulated genes were markedly enriched in inflammati on.related biological processes,as well as in the tumor necrosis factor(TNF)signaling pathway,cytokine-cytokine receptor interactions,complement and coagulation cascades,and in the chemokine signalipathway.Four downregulated genes(collagen type XXVⅢalpha 1 chain[Col28α1],cyclirndependent kinase-like 1[Cdkl1],phosphoserine phosphatase[Psph],and fatty acid desaturase 2[Fads2])and ten upregulated genes(CCAAT/enhancer-binding protein beta[Cebp0],C-X-C motif chemokine receptor 2[Cxcr2],interleukin 11[ll11],C-C motif chemokine ligand 20[Ccl20],nuclear factor-kappa-B inhibitor alpha[NfKbia],claudin 4[Cldn4],matrix metallopeptidase 9[Mmp9],heat shock 70 kDa protein 8[Hspa8],intercellular cell adhesion molecule-1[Icam1],and Jun)were successfully confirmed by real-time polymerase chai n reaction.Wester n blot dem on strated that CDKL1 was decreased,while MMP9 and NFKBIA were increased in the experimental model group compared with those in the sham-operated group.Our study sheds new light on the understand!ng of the early response of the epididymis during bacterial epididymitis.