# Transcriptomic Analysis of the Effects of Hydroxysafflor Yellow A on hUC-MSC Senescence via the ECM–Receptor Interaction Pathway

## TL;DR

This study shows how hydroxysafflor yellow A affects aging stem cells by influencing genes related to cell adhesion and matrix interactions.

## Contribution

The study identifies key genes and pathways through which HSYA impacts senescent hUC-MSCs, particularly the ECM–receptor interaction pathway.

## Key findings

- HSYA treatment altered 2377 genes, mainly linked to cell adhesion and ECM–receptor interactions.
- HSYA reduced senescence markers like β-galactosidase activity and ROS levels in hUC-MSCs.
- Key genes like ID1, SMAD3, and TGFB3 were upregulated, while BMP4 and CCN2 were downregulated.

## 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.