Aloe-Emodin Ameliorates Diabetic Nephropathy by Targeting Interferon Regulatory Factor 4

Abstract

Diabetic nephropathy (DN) is one of the leading causes of end-stage renal disease and lacks effective clinical treatment for its complicated pathogenesis. In this study, the gene expression profiles downloaded from the GEO database were used to identify the key regulatory gene through bioinformatics analyses, and the potential mechanism in regulating DN was revealed via the gene set enrichment analysis, pathway analysis, and in vitro phenotype detection. The effect of the screened drug on DN was analyzed through in vitro and in vivo model experiments. Interferon regulatory factor 4 (IRF4) in DN was identified to be upregulated compared with that in normal control tissues. Further results revealed that IRF4 promoted the DN progression through inflammation, immunity, and extracellular matrix remodeling. The screening results of the TCM library showed that aloe-emodin (Ae) should be a potentially active target drug, and the in vitro and in vivo experiment results demonstrated that Ae could ameliorate DN by targeting IRF4. In conclusion, this study revealed the mechanism of the DN progression and demonstrated that Ae could be a potential target drug in ameliorating DN, providing ideas for the clinical treatments for DN.