Indirubin attenuates mouse psoriasis-like skin lesion in a CD274-dependent manner: an achievement of RNA sequencing
Open Access
- 23 November 2018
- journal article
- research article
- Published by Portland Press Ltd. in Bioscience Reports
- Vol. 38 (6)
- https://doi.org/10.1042/bsr20180958
Abstract
It was previously reported that the expression of CD274 was down-regulated in psoriatic epidermis, leading to immune disorders of psoriasis. However, the regulatory mechanisms of CD274 were rarely elucidated. We aimed to explore the regulatory mechanisms of CD274. Skin samples were collected from 18 patients with psoriasis vulgaris and 9 healthy participants for RNA sequencing. Candidate genes were chosen based on degree and k-core difference of genes in the co-expression network. The relations between candidate genes and CD274 were validated by flow cytometry and real-time PCR in primary human epidermal keratinocytes. The therapeutic effect of indirubin was assessed in an imiquimod-treated mouse model. Interferon-γ (IFN-γ), cyclin-dependent kinase (CDK) 1, Toll-like receptor 3 (TLR3), TLR4 and interleukin (IL)-17A were considered as candidate genes. In primary human epidermal keratinocytes, the level of CD274 was obviously increased under the stimulation of IFN-γ and CDK1 inhibitor (indirubin), independent of TLR4, TLR3 or IL-17A. Indirubin alleviated the severity of psoriatic mice in a CD274-dependent manner. Co-expression network analysis served as an effective method for the exploration of molecular mechanisms. We demonstrated for the first time that CD274 was the regulator of indirubin-mediated effect on mouse psoriasis-like skin lesion based on co-expression network analysis, contributing to the alleviation of mouse psoriasis-like skin lesion.Keywords
This publication has 45 references indexed in Scilit:
- Transcriptional Profiling of Psoriasis Using RNA-seq Reveals Previously Unidentified Differentially Expressed GenesJournal of Investigative Dermatology, 2012
- Indirubin inhibits tumor growth by antitumor angiogenesis via blocking VEGFR2‐mediated JAK/STAT3 signaling in endothelial cellInternational Journal of Cancer, 2011
- Differential expression analysis for sequence count dataGenome Biology, 2010
- TLR3-Stimulated Dendritic Cells Up-regulate B7-H1 Expression and Influence the Magnitude of CD8 T Cell Responses to Tumor VaccinationThe Journal of Immunology, 2009
- RNA-Seq: a revolutionary tool for transcriptomicsNature Reviews Genetics, 2009
- Human Gene Coexpression Landscape: Confident Network Derived from Tissue Transcriptomic ProfilesPLOS ONE, 2008
- -Core Organization of Complex NetworksPhysical Review Letters, 2006
- Psoriasis vulgaris: cutaneous lymphoid tissue supports T-cell activation and ‘Type 1’ inflammatory gene expressionTrends in Immunology, 2004
- Network biology: understanding the cell's functional organizationNature Reviews Genetics, 2004
- KEGG: Kyoto Encyclopedia of Genes and GenomesNucleic Acids Research, 2000