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Journal Article Ppublish 18 citations

PubMed: 36374433 DOI: 10.1007/s10067-022-06400-y

Transcriptional expression of CXCL10 and STAT1 in lupus nephritis and the intervention effect of triptolide.

Clin Rheumatol 42(2):539-548

Authors: Dongliang Shi, Yan Li, Xiaomei Shi, Meihong Yao, Dan Wu, Yuhui Zheng, Qing Lin, Yinghong Yang

Affiliations

  • Department of Pathology, Fujian Medical University Union Hospital, Fuzhou, China.
  • Department of Breast Surgery, Fujian Medical University Union Hospital, Fuzhou, China.
  • Department of Pain Management, Fujian Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China.
  • Department of Clinical Laboratory, The Affiliated People's Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, China.
  • Department of Pathology, Fujian Medical University Union Hospital, Fuzhou, China.

Abstract

OBJECTIVE

This study screened out the key genes associated with the occurrence and development of lupus nephritis (LN) using bioinformatics methods, and then explored the expression of key genes in LN and the inhibitory effect of triptolide.

METHODS

The GEO2R online tool in the GEO database was used to perform differential analysis of gene expression in LN tissues and normal kidney tissues. The GO function and KEGG pathway enrichment analysis of differentially expressed genes (DEGs), STRING, and Cytoscape software were used to build a protein-protein interaction network (PPI) to screen out the Hub gene. Mouse glomerular mesangial cells (MMC) were randomly divided into a control group, an interferon-γ (IFN-γ) stimulation group, and a triptolide intervention group. The relative expression of CXCL10 mRNA in each group was detected by real-time fluorescent quantitative PCR (RT-PCR). CXCL10 secretion was detected by enzyme-linked immunosorbent assay (ELISA), and Western blot was used to detect the expression of the JAK/STAT1 signaling pathway-related proteins STAT1 and p-STAT1 in each group.

RESULTS

Bioinformatics showed that there were 22 DEGs expression differences in the GEO database. The GO enrichment analysis showed that biological process (BP) such as the type I interferon signaling pathway, innate immune response, IFN-γ-mediated signaling pathway, virus defense response, and immune response were significantly regulated by DEGs. Through the combination of String database analysis and cytoscape software, it was found that STAT1 and CXCL10 are closely related to LN. Experimental results showed that IFN-γ induces the expression of CXCL10 mRNA and protein by activating the JAK/STAT1 signaling pathway, while triptolide inhibits the expression of CXCL10 mRNA and protein by inhibiting the JAK/STAT1 signaling pathway.

CONCLUSION

STAT1 and CXCL10 are the key genes in the occurrence and development of LN. IFN-γ induces the expression of CXCL10 by activating the JAK/STAT1 signaling pathway, while triptolide inhibits the expression of CXCL10 by blocking the JAK/STAT1 signaling pathway. Inhibition of the JAK/STAT1 signaling pathway and CXCL10 expression is expected to become a potential target for the treatment of LN. Key Points • Bioinformatics showed that there were 22 DEGs expression differences in the GEO database. • Through the combination of String database analysis and Cytoscape software, it was found that STAT1 and CXCL10 are closely related to LN. • Experimental results showed that IFN-γ induces the expression of CXCL10 mRNA and protein by activating the JAK/STAT1 signaling pathway, while triptolide inhibits the expression of CXCL10 mRNA and protein by inhibiting the JAK/STAT1 signaling pathway.

MeSH

Genes, Rheumatology, Enzyme-Linked Immunosorbent Assay, Lupus Nephritis, Immunity, Software, Tissues, Nephritis

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