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Integrative bioinformatics and experimental analysis reveals FRA1 as a key mediator of tubulointerstitial inflammation in lupus nephritis
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DOI：10.3892/mmr.2026.13813.png)
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Abstract
En 中文
Tubulointerstitial injury is a key driver of lupus nephritis (LN) progression, and dysregulation of the immune microenvironment is a central feature of this process. The molecular mediators of this dysregulation remain incompletely defined. In the present study an integrated bioinformatics and experimental analysis was performed of the Activator Protein 1 (AP-1) family transcription factor Fos-related antigen 1 (FRA1) in LN tubulointerstitium. Analysis of gene expression omnibus datasets (GSE113342, GSE200306 and GSE127797) showed that FRA1 was markedly upregulated in the tubulointerstitium of LN samples and that its expression positively correlated with CD8+ T cells, regulatory T cells, monocytes, M1 macrophages and activated mast cells, but negatively correlated with plasma cells, resting CD4+ memory T cells, M0/M2 macrophages, resting dendritic cells and resting mast cells. In vivo experiments revealed that, FRA1 expression was also increased in kidneys from MRL/lpr mice. Furthermore, in vitro, lentiviral overexpression of FRA1 in HK-2 cells induced robust upregulation of IL-6, IL-1 beta, IL-8, MCP-1 and RANTES, whereas FRA1 knockdown selectively decreased IL-6 and RANTES levels. Together, these results indicate that FRA1 is significantly elevated in the LN tubulointerstitium and may foster a proinflammatory microenvironment by regulating key cytokines. The FRA1/AP-1 axis therefore represents a potential regulator of renal inflammation in LN and a candidate therapeutic target.
Keywords:
lupus nephritis
FRA1
AP-1
transcription factor
tubulointerstitial inflammation
cytokines
immune infiltration
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