Open Access

PTP1B inhibition ameliorates inflammatory injury and dysfunction in ox‑LDL‑induced HUVECs by activating the AMPK/SIRT1 signaling pathway via negative regulation of KLF2

  • Authors:
    • Yunfeng Zhang
    • Qiang Guan
    • Zhenfeng Wang
  • View Affiliations

  • Published online on: May 25, 2022     https://doi.org/10.3892/etm.2022.11394
  • Article Number: 467
  • Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Atherosclerosis is a key pathogenic factor of cardiovascular diseases. However, the role of protein tyrosine phosphatase 1B (PTP1B) in oxidized low‑density lipoprotein (ox‑LDL)‑treated vascular endothelial cells remains unclear. The aim of the present study was to explore the possible physiological roles and mechanism of PTP1B in atherosclerosis using HUVECs as an in vitro model. PTP1B expression was assessed by reverse transcription‑quantitative PCR. Cell viability was measured using the Cell Counting Kit‑8 and lactate dehydrogenase activity assays. Levels of inflammatory factors, including IL‑1β, IL‑6 and TNF‑α, and oxidative stress factors, including malondialdehyde, superoxide dismutase and glutathione peroxidase, were assessed using ELISA and commercially available kits, respectively. Furthermore, TUNEL assay and western blotting were performed to assess the extent of apoptosis‑related factors, including Bcl‑2, Bax, Cleaved caspase‑3 and Caspase‑3. Tube formation assay was used to assess tubule formation ability and western blotting was to analyze VEGFA protein level. Binding sites for the transcription factor Kruppel‑like factor 2 (KLF2) on the PTP1B promoter were predicted using the JASPAR database and verified using luciferase reporter assays and chromatin immunoprecipitation. The protein levels of phosphorylated 5'AMP‑activated protein kinase (p‑AMPK), AMPK and SIRT1 were measured using western blotting. The results demonstrated that the PTP1B mRNA and protein expression levels were significantly upregulated in oxidized low‑density lipoprotein (ox‑LDL)‑induced HUVECs. In addition, ox‑LDL‑induced HUVECs transfected with short hairpin RNA against PTP1B exhibited a significant increase in cell viability, reduced inflammatory factor levels, apoptosis and oxidative stress, as well as increased tubule formation ability. KLF2 was found to negatively regulate the transcriptional activity of PTP1B. KLF2 knockdown reversed the protective effects of PTP1B knockdown on ox‑LDL‑induced HUVECs. KLF2 knockdown also abolished PTP1B knockdown‑triggered AMPK/SIRT1 signaling pathway activation in ox‑LDL‑induced HUVECs. To conclude, the results of the present study suggested that PTP1B knockdown can prevent ox‑LDL‑induced inflammatory injury and dysfunction in HUVECs, which is regulated at least in part by the AMPK/SIRT1 signaling pathway through KLF2.
View Figures
View References

Related Articles

Journal Cover

July-2022
Volume 24 Issue 1

Print ISSN: 1792-0981
Online ISSN:1792-1015

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Zhang Y, Guan Q and Wang Z: PTP1B inhibition ameliorates inflammatory injury and dysfunction in ox‑LDL‑induced HUVECs by activating the AMPK/SIRT1 signaling pathway via negative regulation of KLF2. Exp Ther Med 24: 467, 2022
APA
Zhang, Y., Guan, Q., & Wang, Z. (2022). PTP1B inhibition ameliorates inflammatory injury and dysfunction in ox‑LDL‑induced HUVECs by activating the AMPK/SIRT1 signaling pathway via negative regulation of KLF2. Experimental and Therapeutic Medicine, 24, 467. https://doi.org/10.3892/etm.2022.11394
MLA
Zhang, Y., Guan, Q., Wang, Z."PTP1B inhibition ameliorates inflammatory injury and dysfunction in ox‑LDL‑induced HUVECs by activating the AMPK/SIRT1 signaling pathway via negative regulation of KLF2". Experimental and Therapeutic Medicine 24.1 (2022): 467.
Chicago
Zhang, Y., Guan, Q., Wang, Z."PTP1B inhibition ameliorates inflammatory injury and dysfunction in ox‑LDL‑induced HUVECs by activating the AMPK/SIRT1 signaling pathway via negative regulation of KLF2". Experimental and Therapeutic Medicine 24, no. 1 (2022): 467. https://doi.org/10.3892/etm.2022.11394