Involvement of TLR2/4‑MyD88‑NF‑κB signaling pathway in the pathogenesis of intracranial aneurysm

Zhang,Xuezhi; Wan,Yilv; Feng,Jiugeng; Li,Meihua; Jiang,Zhiqun

doi:10.3892/mmr.2021.11869

Involvement of TLR2/4‑MyD88‑NF‑κB signaling pathway in the pathogenesis of intracranial aneurysm

Authors:
- Xuezhi Zhang
- Yilv Wan
- Jiugeng Feng
- Meihua Li
- Zhiqun Jiang
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Affiliations: Department of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China
Published online on: January 26, 2021 https://doi.org/10.3892/mmr.2021.11869
Article Number: 230

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Abstract

Toll‑like receptor (TLR) 2/4 serves an important regulatory role in nerve tissue injury. However, the downstream and potential mechanisms remain to be elucidated. The present study was designed to investigate the roles of the TLR2/4‑major myeloid differentiation response gene 88 (MyD88)‑NF‑κB signaling pathway in the development of intracranial aneurysm. The expression of TLR2, TLR4 and MyD88 in the blood of normal controls and patients with intracranial aneurysm were detected by quantitative PCR and ELISA. Human brain vascular smooth muscle cells were treated by Angiotensin II (Ang II) to evaluate the involvement of TLR2/4‑MyD88‑NF‑κB signaling pathway in the process. The in vitro experiment was divided into four groups: The control group, an Ang Ⅱ group, an Ang Ⅱ + small interfering (si)RNA control group and an Ang Ⅱ + TLR2‑group. Cell viability, migration, apoptosis and expression of TLR2, TLR4, MyD88, NF‑κB and phosphorylated (p‑)p65 expression were detected. The results demonstrated that the expression of TLR2, TLR4, MyD88 and NF‑κB at mRNA and protein levels in patients with intracranial aneurysm was significantly higher compared with corresponding protein in normal controls (P<0.05). In vitro experiments demonstrated that Ang Ⅱ treatment increased the cell proliferation and migration rate but reduced the apoptotic rate compared with the control (P<0.05). The expression of TLR2, TLR4, MyD88, NF‑κB and p‑p65 was significantly increased in the Ang II group (vs. control; P<0.05). By contrast, TLR2‑short interfering RNA reduced the cell proliferation and migration rate, and reduced the expression of TLR2, TLR4, MyD88, NF‑κB and p‑p65 (vs. Ang Ⅱ + short interfering RNA control; P<0.05). In conclusion, the data of the present study indicated that the TLR2/4‑MyD88‑NF‑κB signaling pathway is involved in the pathogenesis of intracranial aneurysm.

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