Uric acid induces the expression of TNF‑α via the ROS‑MAPK‑NF‑κB signaling pathway in rat vascular smooth muscle cells

Tang,Lirong; Xu,Yu'e; Wei,Ying; He,Xu

doi:10.3892/mmr.2017.7405

Uric acid induces the expression of TNF‑α via the ROS‑MAPK‑NF‑κB signaling pathway in rat vascular smooth muscle cells

Authors:
- Lirong Tang
- Yu'e Xu
- Ying Wei
- Xu He
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Affiliations: Department of Pharmacy, Hanzhong Central Hospital, Hanzhong, Shaanxi 723000, P.R. China, Department of Physical Education, Shaanxi University of Technology, Hanzhong, Shaanxi 723001, P.R. China
Published online on: August 31, 2017 https://doi.org/10.3892/mmr.2017.7405
Pages: 6928-6933

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Abstract

Hyperuricemia and artery atherosclerosis are closely associated and, as a classic inflammatory biomarker, tumor necrosis factor‑α (TNF‑α) has a direct role in atherogenesis. In the present study, it was demonstrated that uric acid was capable of inducing the generation of TNF‑α in vascular smooth muscle cells (VSMCs). The expression levels of proteins were detected using enzyme‑linked immunosorbent assays and western blot analysis. The expression levels of mRNAs were determined using reverse transcription‑quantitative polymerase chain reaction analysis, and superoxide anion levels were detected using a fluorescence microscope. From the results, it was concluded that uric acid induced the expression of TNF‑α in the VSMCs. The antioxidant, N‑acetylcysteine, eliminated the uric acid‑induced expression of TNF‑α. In addition, uric acid increased the level of reactive oxygen species (ROS) and activated the phosphorylation of p38. Subsequent experiments confirmed that the p38 mitogen‑activated protein kinase (MAPK) inhibitor, SB203580, and nuclear factor (NF)‑κB inhibitor, pyrrolidine dithiocarbamate, eliminated the uric acid‑induced expression of TNF‑α. It was demonstrated that uric acid induced the expression of TNF‑α via the ROS‑MAPK‑NF‑κB signaling pathway in VSMCs, providing novel evidence supporting the pro‑inflammatory and pro‑atherosclerotic effects of uric acid.

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