Increased Cthrcl Activates Normal Fibroblasts and Suppresses Keloid Fibroblasts by Inhibiting TGF-β/Smad Signal Pathway and Modulating YAP Subcellular Location

Keloid may induce severe impairment of life quality for the patients,although keloid is a cutaneous benign tumor.Collagen triple helix repeat containing protein 1 (Cthrc1) was identified as a novel gene that was originally found in adventitial fibroblasts after arterial injury.To address the role of Cthrcl in keloid,the expression level of Cthrcl was assessed in normal skin and keloid tissue,as well as in normal fibroblasts (NFs)and keloid fibroblasts (KFs)by using quantitative PCR,Western blotting and immunohistochemical analysis.The results showed that Cthrcl was increased in keloid tissue and KFs as compared with normal skin and NFs.Meanwhile,CCK8 and Transwell assays found the cellular proliferation and migration of KFs were increased as compared with NFs.Further,to verify the function of Cthrcl in NFs and K.Fs,we increased Cthrcl expression by transfecting lentivirns (LV) vectors LV-Cthrcl.The cellular proliferation and migration,collagen synthesis and the influence on TGF-β and YAP signaling were tested.The cellular proliferation and migration were increased in NFs-Cthrcl as compared with NFs-control.Meanwhile,YAP expression and nuclear-location was increased in NFs-Cthrcl.On the contrary,when Cthrcl was overexpressed in KFs,the cellular migration was suppressed and YAP expression was reduced and transferred to cytoplasm in KFs-Cthrcl as compared with KFs-control.But the expression level of collagen I was decreased and pSmad2/3 nucleus transfer was suppressed in both NFs-Cthrc1 and KFs-Cthrc1 by using Western blotting and immunofluorescence.Increased Cthrcl activated NFs by promoting YAP nucleus translocation,whereas suppressed KFs by inhibiting YAP nucleus translocation.Enhanced Cthrcl decreased collagen I in both NFs and KFs by inhibiting TGF-β/Smad pathway.In conclusion,Cthrcl may play a role in the pathogenesis of keloid by inhibiting collagen synthesis and fibroblasts migration via suppressing TGF-β/Smad pathway and YAP nucleus translocation.

Identification and Interaction Analysis of Key Genes and MicroRNAs in Systemic Sclerosis by Bioinformatics Approaches

Systemic sclerosis (SSc) is a highly heterogeneous autoimmune disease with a high mortality rate.However,the cellular and molecular mechanisms of SSc remain unclear.Here,we identified the key hub genes and microRNAs (miRNAs) that modulate the occurrence and development of SSc.We downloaded the microarray dataset GSE95065 from the Gene Expression Omnibus (GEO) database and then analyzed the data by using GEO2R.The Database for Annotation,Visualization and Integrated Discovery (DAVID) was used for functional pathway enrichment analyses of differentially expressed genes (DEGs),and Cytoscape software was used to generate the protein-protein interaction (PPI) network.In addition,OmicsNet was used to predict the miRNAs for the hub genes of SSc.As a result,783 DEGs were identified,of which 770 genes (142 up-regulated genes and 628 down-regulated genes) were matched to the genes in SSc skin samples.Gene Ontology (GO) analyses by DAVID indicated that the up-regulated genes were mainly involved in immune response,and the down-regulated genes were greatly enriched in glycinergic synaptic transmission.In the PPI network,22 nodes were selected as key genes,including several members of the chemokine family.Furthermore,after uploading these key genes to the OmicsNet tool,we found that hsa-miR-26b-5p might target CXCL9 and CXCL13.Moreover,we demonstrated that the hsa-miR-26b-5p inhibitor might inhibit fibrosis in TGF-β-activated fibroblasts,which would be a promising target for SSc therapy.

Pathogen Analysis of Superficial Mucocutaneous Mycosis in a Tertiary A-level Hospital from 2007 to 2018

Objective This study aimed to analyze the fungal species of pathogens isolated from patients with superficial mucocutaneous mycosis from May 2007 to December 2018.Methods A retrospective analysis was carried out to determine the pathogenic fungi isolated from patients with superficial fungal infections in the Medical Mycology Clinical Laboratory,Department of Dermatology and Venereology,Union Hospital,from May 2007 to December 2018.Results A total of 7639 strains were obtained,belonging to 21 genera and 36 species.They mainly consisted of Candida(3707/7639,48.53%)and dermatophytes(3594/7639,47.05%).The specimens were skin scales,nail shavings,secretions on the nail grooves,broken or diseased hair and dandruff,secretions or pseudomembrane of the external genitalia,and the oral mucosa.A total of 7300 patients were enrolled in this study,including 3301 males and 3999 females aged 2 months to 92 years old with a median age of 46.04 years old except for 633 patients whose ages were unknown.Two strains of different species were isolated from each of 339 patients at different body sites.The most frequent species were Trichophyton rubrum complex(2906/7639,38.04%),Candida albicans(2619/7639,34.28%),and unclassified Candida spp.Dermatophytes were mostly isolated from glabrous skin(2138/3594,59.49%),with T.rubrum complex being the predominant species.Candida strains were most commonly isolated from mucosal sites(1979/3707,53.39%),and C.albicans was the most prevalent causative agent.Conclusion The main distribution of pathogenic fungal species isolated from patients with superficial mycosis from 2007 to 2018 in Wuhan,Hubei province and the surrounding areas was that Candida slightly outnumbered dermatophytes.Among all of the isolated strains,T.rubrum complex was the most abundant.