Yan Ke, Bian Jiarong, He Liang, Song Bingwei, Shen Linhai, Zhen Yong
Department of Neurosurgery, Clinical Medical College of Yangzhou University, Northern Jiangsu People's Hospital, No. 98 Nantong West Road, Yangzhou, 225001, China.
Department of Respiratory Medicine, Clinical Medical College of Yangzhou University, Northern Jiangsu People's Hospital, Yangzhou, 225001, China.
Biochem Genet. 2024 Dec;62(6):4837-4850. doi: 10.1007/s10528-024-10681-0. Epub 2024 Feb 18.
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 HO-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 HO 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 HO-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.
血管平滑肌细胞（VSMCs）影响颅内动脉瘤（IA）的表型变化。它们表现出增强的解离和迁移，并在IA发病机制中起关键作用。KLF转录因子11（KLF11）是KLF家族的成员，显著影响癌细胞的增殖、分化和凋亡。然而，其在IA中的表达、生物学功能和潜在作用机制仍不清楚。本研究旨在分析KLF11对IA中血红素加氧酶（HO）诱导的人脑血管平滑肌细胞（HBVSMCs）的影响。我们测定了15对IA患者和健康志愿者动脉壁组织中KLF11的mRNA水平。用HO刺激HBVSMCs 6小时以在体外建立IA模型。分别使用3-（4,5-二甲基噻唑-2-基）-2,5-二苯基四氮唑溴盐、流式细胞术和酶联免疫吸附测定法评估细胞活力、凋亡和炎性细胞因子（白细胞介素[IL-1β、肿瘤坏死因子-α和IL-6]）水平。通过定量逆转录-聚合酶链反应、蛋白质印迹和免疫荧光分析确定KLF11表达。此外通过蛋白质印迹法测定磷酸化p38、p38、裂解的半胱天冬酶3和半胱天冬酶3水平。与对照组相比，IA患者动脉壁组织中的KLF11水平下调。KLF11质粒上调KLF11可促进细胞活力、减少凋亡、降低裂解的半胱天冬酶3表达，并抑制HO诱导的HBVSMCs中炎性因子的分泌。KLF11质粒显著降低磷酸化p38表达和磷酸化p38/ p38比率；然而，P79350处理可逆转这些作用。总体而言KLF11上调改善了HBVSMC功能并对IA发挥保护作用，表明其在IA治疗中的潜力。
