Transcriptomic Analysis of the Effects of Hydroxysafflor Yellow A on hUC-MSC Senescence via the ECM-Receptor
Siyun Wang1, Qi Zhu1, Xueer Feng1
1School of Life Science, Beijing University of Chinese Medicine, Beijing 102488, China.
Abstract:
This study investigated the mechanism of hydroxysafflor yellow A (HSYA) on senescent human umbilical cord mesenchymal stem cells (hUC-MSCs) through transcriptome sequencing. HSYA treatment identified 2377 differentially expressed genes (DEGs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that these DEGs were primarily enriched in cell adhesion regulation and the extracellular matrix (ECM)-receptor interaction pathway. Gene Set Enrichment Analysis (GSEA) and protein-protein interaction (PPI) network analysis corroborated the central role of ECM-receptor interaction signaling, and Key Driver Analysis (KDA) revealed 10 core regulatory genes (e.g., ID1, SMAD3, TGFB3). SA-β-gal staining showed that HSYA significantly reduced senescence-associated β-galactosidase activity. Flow cytometry showed no significant changes in cell cycle distribution. Western blot analysis indicated that HSYA treatment reduced the protein expression level of p16 without significantly altering p53 levels. Furthermore, HSYA significantly attenuated intracellular reactive oxygen species (ROS) accumulation. qPCR validation demonstrated that HSYA significantly upregulated ID1, GDF5, SMAD3, and TGFB3 while downregulating BMP4, TGFB2, and CCN2. These findings indicate that HSYA modulates genes associated with the ECM-receptor interaction pathway, potentially contributing to improved ECM homeostasis in senescent hUC-MSCs.
