ETS proto-oncogene 1 modulates PTP1B expression to participate in high glucose-mediated endothelial inflammation.

Abstract

Hyperglycemia-induced endothelial inflammation participates in the pathogenesis of cardiovascular complications in diabetics. Previous studies showed that protein tyrosine phosphatase 1B (PTP1B) and ETS proto-oncogene 1 (ets1) are involved in hyperglycemia-induced endothelial inflammation. In this study, we hypothesized that ets1 modulates PTP1B expression, thus playing a crucial role in hyperglycemia-induced vascular endothelial inflammation. Our results indicated that high glucose increases monocyte/endothelial adhesion, vascular cell adhesion molecule-1 (VCAM-1) expression and p65 phosphorylation in human umbilical vein endothelial cells (HUVECs). Moreover, high glucose-mediated endothelial inflammation is reversed by PTP1B silencing. In addition, high glucose increases ets1 expression in HUVECs. silencing reverses high glucose-mediated endothelial inflammation. Furthermore, the effect of ets1 overexpression is similar to that of high glucose treatment, which is counteracted by si-PTP1B. The results from ChIP assays indicated that ets1 occupies the PTP1B promoter region. Ets1 overexpression enhances PTP1B promoter activity, which is disappeared after specific binding site mutation. experiments demonstrated that the expressions of VCAM-1, PTP1B, and ets1, as well as the phosphorylation of p65 are augmented in the aorta of diabetic rats. In conclusion, ets1 contributes to hyperglycemia-mediated endothelial inflammation via upregulation of PTP1B expression.

• Authors: Lili Jiang, Jincai Liang, Tianhai Wang, Fufen Meng, Wenming Duan
• Journal: Acta biochimica et biophysica Sinica (Acta Biochim Biophys Sin (Shanghai)) Vol. 54 Issue 4 Pg. 565-573 (Apr 25 2022) ISSN: 1745-7270 [Electronic] China
• PMID: 35607953 (Publication Type: Journal Article)

Chemical References

• ETS1 protein, human
• Proto-Oncogene Protein c-ets-1
• Vascular Cell Adhesion Molecule-1
• Phosphoric Monoester Hydrolases
• PTPN1 protein, human
• Protein Tyrosine Phosphatase, Non-Receptor Type 1
• Glucose

Topics

• Animals
• Diabetes Mellitus, Experimental (genetics, metabolism)
• Glucose (metabolism, pharmacology)
• Human Umbilical Vein Endothelial Cells (metabolism)
• Humans
• Hyperglycemia (genetics, metabolism)
• Inflammation (genetics, metabolism)
• Phosphoric Monoester Hydrolases (metabolism)
• Protein Tyrosine Phosphatase, Non-Receptor Type 1 (genetics)
• Proto-Oncogene Protein c-ets-1 (genetics)
• Proto-Oncogenes
• Rats
• Vascular Cell Adhesion Molecule-1 (genetics, metabolism)