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Effects of KLF11 on Vascular Smooth Muscle Cells and its Underlying Mechanisms in Intracranial Aneurysm

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Abstract

Vascular smooth muscle cells (VSMCs) affect the phenotypic changes in intracranial aneurysm (IA). They exhibit enhanced dissociation and migration and play a key role in IA pathogenesis. KLF transcription factor 11 (KLF11), a member of the KLF family, significantly affects the cancer cell proliferation, differentiation, and apoptosis. However, its expression, biological functions, and latent action mechanisms in IA remain unclear. This study aimed to analyze the effects of KLF11 on H2O2-induced human brain VSMCs (HBVSMCs) in IA. We determined the mRNA levels of KLF11 in 15 paired arterial wall tissues of patients with IA and healthy volunteers. HBVSMCs were stimulated with H2O2 for 6 h to establish an IA model in vitro. Cell viability, apoptosis, and inflammatory cytokine (interleukin [IL-1β, tumor necrosis factor-α, and IL-6) levels were assessed using the 3-(4,5-dimethylthiazol-2-yl)-2–5-diphenyltetrazolium bromide, flow cytometry, and enzyme-linked immunosorbent assays, respectively. KLF11 expression was determined via quantitative reverse transcription-polymerase chain reaction, western blotting, and immunofluorescence analyses. Furthermore, p-p38, p38, cleaved-caspase 3, and caspase 3 levels were determined via western blotting. KLF11 levels were downregulated in the arterial wall tissues of patients with IA than in those of the control group. KLF11 upregulation by KLF11-plasmid promoted the cell viability, reduced apoptosis, decreased cleaved-caspase 3 expression, and inhibited the secretion of inflammatory factors in H2O2-induced HBVSMCs. KLF11-plasmid remarkably reduced p-p38 expression and p-p38/p-38 ratio; however, these effects were reversed by P79350 treatment. Overall, KLF11 upregulation improved the HBVSMC functions and exerted protective effects against IA, suggesting its potential for IA treatment.

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Data Availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

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Funding

The present study was supported by the Key R&D Program of Yangzhou city (grant no. YZ2021089).

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Authors and Affiliations

  1. Department of Neurosurgery, Clinical Medical College of Yangzhou University, Northern Jiangsu People’s Hospital, No. 98 Nantong West Road, Yangzhou, 225001, China

    Ke Yan, Liang He, Bingwei Song, Linhai Shen & Yong Zhen

  2. Department of Respiratory Medicine, Clinical Medical College of Yangzhou University, Northern Jiangsu People’s Hospital, Yangzhou, 225001, China

    Jiarong Bian

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  1. Ke Yan
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  2. Jiarong Bian
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  3. Liang He
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  4. Bingwei Song
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  5. Linhai Shen
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  6. Yong Zhen
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Contributions

YZ conceived and designed the experiments; YZ, KY, LH, BS, and LS performed the experiments; YZ, KY, and JB analyzed the data; YZ, KY, and JB contributed to writing-original draft. YZ contributed to writing-review & editing. All authors have read and approved the final manuscript.

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Correspondence to Yong Zhen.

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The authors declare that they have no competing interests.

Ethical Approval

The study protocol was approved by the Ethics Committee of the Clinical Medical College of Yangzhou University Northern Jiangsu Province Hospital.

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Informed consent was obtained from all individual participants included in the study.

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The authors affirm that human research participants provided informed consent for publication of the images in Fig. 1.

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Yan, K., Bian, J., He, L. et al. Effects of KLF11 on Vascular Smooth Muscle Cells and its Underlying Mechanisms in Intracranial Aneurysm. Biochem Genet (2024). https://doi.org/10.1007/s10528-024-10681-0

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