FOXP1‑induced DUSP12 alleviates vascular endothelial cell inflammation and oxidative stress injury induced by ox‑LDL via MAP3K5 signaling pathway

Li,Yuanmin; Gu,Long; Zhou,Jian; Han,Chenjun; Zang,Wangfu

doi:10.3892/etm.2023.12149

FOXP1‑induced DUSP12 alleviates vascular endothelial cell inflammation and oxidative stress injury induced by ox‑LDL via MAP3K5 signaling pathway

Authors:
- Yuanmin Li
- Long Gu
- Jian Zhou
- Chenjun Han
- Wangfu Zang
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Affiliations: Department of Cardio‑Thoracic Surgery, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, P.R. China, Department of Blood Transfusion, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, P.R. China, Department of Cardio‑Thoracic Surgery, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, P.R. China
Published online on: August 3, 2023 https://doi.org/10.3892/etm.2023.12149
Article Number: 450
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Atherosclerosis (AS) is a type of chronic inflammatory disease and the main pathological basis of cardiovascular and cerebrovascular diseases, which seriously threaten the health of patients. The dual specificity phosphatase 12 (DUSP12) protein is known as regulator of inflammatory diseases. Nonetheless, at present, there are only a few reports on the regulatory role of DUSP12 in AS. Human umbilical vein endothelial cells (HUVECs) were induced using oxidized low‑density lipoprotein (ox‑LDL). Subsequently, cell transfection experiments were performed to overexpress DUSP12 in ox‑LDL‑induced HUVECs. Cell Counting Kit‑8, TUNEL western blotting, 2',7'‑dichlorofluorescein diacetate assays, ELISA and other techniques were used to measure cell viability, apoptosis, inflammation, oxidative stress and endothelial function‑related indicators. Subsequently, the relationship between DUSP12 and Forkhead box P1 (FOXP1) was predicted using the JASPAR database and verified using luciferase reporter and chromatin immunoprecipitation assays. Finally, the regulatory mechanism was investigated by simultaneously overexpressing DUSP12 and knocking down FOXP1 in ox‑LDL‑induced HUVECs and MAP3K5‑related proteins of the DUSP12 downstream pathway were measured by western blotting. The expression of DUSP12 in ox‑LDL‑induced HUVECs was significantly decreased. Overexpression of DUSP12 inhibited apoptosis, inflammation and oxidative stress damage and alleviated endothelial dysfunction in ox‑LDL‑induced HUVECs. FOXP1 promoted the transcription of DUSP12. Moreover, FOXP1 alleviated ox‑LDL‑induced apoptosis, inflammation and oxidative stress damage in HUVECs by regulating the expression of DUSP12, probably acting through the MAP3K5 pathway. Collectively, the present study revealed that FOXP1‑induced DUSP12 alleviated vascular endothelial cell inflammation and oxidative stress injury in ox‑LDL‑induced HUVECs via the MAP3K5 signaling pathway, which might shed novel insights into the targeted treatment for AS in the clinic.

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