Pituitary tumor-transforming gene 1 (PTTG1) has been found to be associated with the process of cell proliferation and invasion, and is highly expressed in aortic dissection (AD). However, its potential role and underlying mechanism in AD remain uncertain. This study aims at elucidating the roles of specificity protein 1 (SP1) and PTTG1 in the migration and phenotypic switching of aortic vascular smooth muscle cells (VSMCs) in AD. Aortic samples were collected from 35 patients with AD for examination of PTTG1 expression in the tissues by qPCR, western blot and immunofluorescence. Human aortic vascular smooth muscle cells (HAVSMCs) were stimulated with platelet-derived growth factor-BB (PDGF-BB) to establish the cellular model of AD. PTTG1 expression in VSMCs was also examined by qPCR and western blot. Cell viability was detected by CCK-8, cell proliferation by EdU staining and cell migration by wound healing and transwell. Western blot was then performed to assay migration-related proteins. After interference with PTTG1, the levels of smooth muscle pthenotypic switch markers smooth muscle protein 22 alpha (SM22-α) and osteopontin (OPN) were detected by qPCR, western blot and immunofluorescence. The binding of SP1 and PTTG1 was verified with dual-luciferase reporter assay and chromatin immunoprecipitation assay (ChIP). PTTG1 overexpression was found in AD patients. Interference with PTTG1 attenuated the proliferation and migration of PDGF-BB-stimulated HAVSMCs, in addition to their switching from contractile phenotype to synthetic phenotype. Transcription factor SP1 was up-regulated in PDGF-BB-stimulated HAVSMCs, combined with PTTG1 promoter sequence and regulated PTTG1 expression, whose overexpression reversed the effects of PTTG1 interference on cell proliferation, migration and phenotypic switching. SP1 transcriptional activation of PTTG1 activated MAPK/ERK signaling pathway. In conclusion, SP1 transcriptional activation of PTTG1 regulates the migration and phenotypic transformation of HAVSMCs in AD by MAPK Signaling.

垂体肿瘤转化基因 1 (PTTG1) 已被发现与细胞增殖和侵袭过程有关，并且在主动脉夹层 (AD) 中高度表达。然而，其在 AD 中的潜在作用和潜在机制仍不确定。本研究旨在阐明特异性蛋白 1 (SP1) 和 PTTG1 在 AD 中主动脉血管平滑肌细胞 (VSMC) 迁移和表型转换中的作用。从 35 名 AD 患者收集主动脉样本，通过 qPCR、蛋白质印迹和免疫荧光检查组织中 PTTG1 的表达。用血小板衍生生长因子-BB (PDGF-BB) 刺激人主动脉血管平滑肌细胞 (HAVSMCs) 以建立 AD 细胞模型。还通过 qPCR 和蛋白质印迹检查了 VSMC 中 PTTG1 的表达。CCK-8检测细胞活力，EdU 染色的细胞增殖和伤口愈合和 transwell 的细胞迁移。然后进行蛋白质印迹以测定迁移相关蛋白。干扰PTTG1后，通过qPCR、蛋白质印迹和免疫荧光检测平滑肌表型转换标志物平滑肌蛋白22α（SM22-α）和骨桥蛋白（OPN）的水平。SP1 和 PTTG1 的结合通过双荧光素酶报告基因测定和染色质免疫沉淀测定 (ChIP) 进行验证。在 AD 患者中发现了 PTTG1 过表达。对 PTTG1 的干扰减弱了 PDGF-BB 刺激的 HAVSMCs 的增殖和迁移，以及它们从收缩表型到合成表型的转换。转录因子 SP1 在 PDGF-BB 刺激的 HAVSMCs 中上调，结合 PTTG1 启动子序列并调节 PTTG1 表达，其过表达逆转了 PTTG1 干扰对细胞增殖、迁移和表型转换的影响。PTTG1 的 SP1 转录激活激活 MAPK/ERK 信号通路。总之，PTTG1 的 SP1 转录激活通过 MAPK 信号调节 AD 中 HAVSMCs 的迁移和表型转化。