Abstract
Lupus nephritis (LN) is an immune-complex nephritis and one of the most severe organ manifestations of systemic lupus erythematosus. To elucidate the mechanisms underlying LN, we firstly performed comprehensive RNA sequencing and microRNA (miRNA) sequencing analyses on the kidneys of female lupus-prone MRL/lpr mice and female C57BL/6 mice. Our results revealed significant renal impairment in 17-week-old female MRL/lpr mice, as evidenced by elevated 24-hour urinary protein, serum creatinine, and blood urea nitrogen levels, along with severe renal pathology. RNA sequencing identified 100 upregulated and 59 downregulated genes in the kidneys of 17-week-old MRL/lpr mice, which were enriched in immune response, transcriptional regulation, and metabolic reprogramming. MiRNA sequencing further identified 23 upregulated and 9 downregulated miRNAs in MRL/lpr mice. Interaction network analysis revealed that the upregulated miRNAs (miR-3473b and miR-204-3p) were linked to transcriptional regulation and DNA repair, while the downregulated miRNA (miR-7213-5p) was closely associated with immune cell trafficking, immune function regulation, and metabolism. Subsequent validation confirmed the significant downregulation of miR-7213-5p in MRL/lpr kidneys, whereas the levels of its predicted target, CC motif chemokine 19 (CCL19), were significantly elevated in both renal fibroblasts and serum. Mechanistically, miR-7213-5p directly targeted the 3'-untranslated region of CCL19, thereby suppressing both the expression and secretion of CCL19 induced by TNF-α in L929 fibroblasts. These findings highlight the anti-inflammatory role of miR-7213-5p via the regulation of CCL19, suggesting its potential as a therapeutic target for LN.