RNA-sequencing analysis reveals the potential mechanism by which a Dioscorea polystachya (Chinese yam) protein ameliorates hyperglycemia-induced endothelial dysfunction

Abstract Background Hyperglycemia-induced endothelial dysfunction is one of the most crucial factors leading to disability and death in patients with diabetes mellitus (DM). Dioscorea polystachya (Chinese yam), a well-known ingredient used in traditional Chinese medicine, contains various bioactive components that have been widely used to treat endothelium-related diseases. The aim of this study was to explore the molecular mechanism and therapeutic targets of the Chinese yam protein DP1 on hyperglycemia-induced endothelial dysfunction. Methods and results We first investigated the effect of DP1 isolated from Chinese yam, on human umbilical vein endothelial cells (HUVECs) that had been exposed to high-glucose (HG, 30 mmol/L) conditions for 48 h. CCK-8 assay showed that DP1 enhanced HUVECs viability. ELISA and tube formation assays indicated that DP1 increased NO levels and promoted angiogenesis by increasing node numbers, mesh numbers, and tube length. Moreover, SA-β-gal staining showed that DP1 inhibited the HG-induced increase in the percentage of senescent cells. RNA-sequencing analysis revealed a total of 335 DEGs between the HG group and the DP1 group. Gene expression profiling showed that NUMBL , AFDN , ITGA6 , ITGB1 , DSP , AGO2 , QKI , FBXW7 , YAP1 , CCBE1 , NCL , SIRT1 , JUND , PRKDC , PTEN , CDK6 , KAT6A , NFATC3 , PPP1CA , and MIF might play key roles in mediating the effects of DP1 treatment on HG-induced endothelial dysfunction by regulating angiogenesis and cellular senescence, and these findings were validated by RT-PCR. Conclusion This study deepens our current knowledge of the molecular effects of DP1 on hyperglycemia-induced endothelial dysfunction and suggests a possible strategy for treating endothelium-related diseases using a Chinese yam protein.