Identification of characteristic genes of pressure ulcers based on angiogenesis-related genes and construction of miRNA, transcription factor, and molecular drug regulatory networks

This study aimed to analyze transcriptomic changes in pressure ulcer (PU) samples, identify angiogenesis-related differentially expressed genes (AR-DEGs), and explore their potential as diagnostic and therapeutic targets for PU, with a particular focus on the role of CDKN1A. Transcriptomic data from dataset GSE137897, which included 381 PU samples and 391 healthy controls, were utilized to investigate these changes. Differential expression analysis was performed to identify AR-DEGs, which were subsequently analyzed for enrichment in regulatory and signaling pathways. Protein-protein interaction (PPI) network analysis was carried out to highlight key hub AR-DEGs. In addition, correlation analysis was performed to examine the relationships between these genes. Regulatory networks involving microRNAs (miRNAs), transcription factors (TFs), and targeted drugs were constructed using miRNet and DGIdb. A rat PU model was established to validate the expression of CDKN1A in vivo and to investigate the effects of CDKN1A knockout on PU healing. Through differential expression analysis, 128 AR-DEGs were identified and found to be enriched in various regulatory and signaling pathways. PPI network analysis identified seven hub AR-DEGs (JUN, HIF1A, CCND1, FOS, HDAC1, CDKN1A, CCL2), which exhibited strong diagnostic potential for PU. Correlation analysis revealed that CDKN1A was negatively correlated with CCND1, CCL2, and FOS, while HIF1A was positively correlated with CDKN1A and HDAC1. Validation experiments in a rat PU model confirmed that CDKN1A was significantly upregulated at both the mRNA and protein levels in wound tissues. Furthermore, silencing CDKN1A in dermal fibroblasts enhanced cell viability, migration (wound healing), and collagen secretion in vitro. In vivo, CDKN1A knockout significantly accelerated wound healing in PU rats, as evidenced by improved wound closure, reduced inflammation, and increased collagen deposition. This study demonstrates that CDKN1A plays a pivotal role in modulating inflammation and collagen synthesis in PUs. The findings suggest that CDKN1A holds promise as a therapeutic target for PU treatment, providing novel insights into the management of this condition.