Aim To investigate the biological function and molecular mechanisms of piRNA-823 in the phenotypic transformation of human umbilical vein endothelial cells(HUVEC)induced by high glucose.Methods HUVEC were incubated in high glucose(33.3 mmol/L)culture medium for 72 h.The relative expression levels of piR-NA-823 were detected by RT-qPCR,the expression changes of endothelial cell markers,mesenchymal cell markers and proteins related to transforming growth factor-β1(TGF-β1)signaling pathway were detected by Western blot,the changes of cell migration ability were evaluated by scratch and Transwell assays,the formation of new angiogenesis were assessed through angiogenesis experiments.piRNA-823 mimic(overexpression of piRNA-823)were transfected into HUVEC to analyze their effects on high glucose induced endothelial-mesenchymal transition(EndMT)and angiogenesis.Further in-tervention was performed using TGF-β1 activator(SRI011381)and inhibitor(SB525334)to verify whether piRNA-823 ex-erts its effect by regulating the TGF-β1/Smad2/3 signaling pathway.Results piRNA-823 mimic significantly inhibited the viability,proliferation,migration and angiogenesis of HUVEC induced by high glucose.The piRNA-823 mimic inhibited high glucose induced EndMT in HUVEC,characterized by upregulation of endothelial cell markers and downregulation of mesenchymal cell markers.Scratch experiments,Transwell experiments and angiogenesis experiments further confirmed that piRNA-823 mimic could effectively reverse high glucose induced HUVEC proliferation,migration a-bility enhancement,and increase in the number of new angiogenesis.Mechanistic studies revealed that the TGF-β1 acti-vator partially reversed the protective effect of piRNA-823 mimic,whereas the TGF-β1 inhibitor enhanced its effect,sug-gesting that piRNA-823 exerts its regulatory role by suppressing the activation of the TGF-β1/Smad2/3 signaling pathway.Conclusion piRNA-823 significantly inhibits high glucose induced EndMT,proliferation,migration and angiogenesis in HUVEC by suppressing the activation of TGF-β1/Smad2/3 signaling pathway.