Single-cell RNA transcriptome analysis reveals regulatory programs of RNA binding proteins in diabetic foot ulcers

单细胞RNA转录组分析揭示糖尿病足溃疡中RNA结合蛋白的调控程序

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Abstract

Diabetic foot ulceration poses a serious threat to the health of patients with diabetes, and its pathogenic mechanism remains unclear. In this study, we analyzed the expression profiles of genes encoding RNA-binding proteins (RBPs) in the foot and peripheral blood mononuclear cells using single-cell sequencing data from GEO database. Our analysis revealed that RBP genes were abnormally expressed in DFUs, highly cell population-specific, and can be used as signature genes for different cell clusters. Co-expression and Gene Ontology enrichment analyses showed that differentially expressed RBP genes were highly related to the wound healing process. Genes encoding heat shock proteins were associated with 'healing-related' fibroblast differentiation. Western blotting of wound tissues from normal control and diabetic patients were performed, confirming the significant upregulation of HSP90 and downregulation of ZFP36. Analysis of the combined foot samples and peripheral blood mononuclear cell samples revealed common differentially expressed RBP genes, indicating consistency between foot and blood samples. Our results demonstrate the important roles of RBP in the healing process of chronic diabetic wounds, provide clues for further research on RBP regulatory mechanisms in certain cell types, and help develop novel therapeutic treatments for DFUs.

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