Department of Cardiac Surgery, Fuwai Hospital Chinese Academy of Medical Sciences Shenzhen, Shenzhen, Guangdong 518057, P.R. China.
Mol Med Rep. 2021 Jan;23(1). doi: 10.3892/mmr.2020.11703. Epub 2020 Nov 20.
Extracellular matrix (ECM) proteins serve a major role in the pathogenesis of aortic dissection (AD). The aim of the present study was to investigate the effect of osteoglycin (OGN), an ECM proteoglycan, on aortic dissection (AD), as well as the underlying mechanism. Thoracic aortic tissues from 20 patients with AD and healthy thoracic aortic tissue from 5 patients undergoing coronary artery bypass grafting were collected to detect OGN expression levels. Following OGN knockdown in rat aortic smooth muscle cells, cell proliferation was detected by performing Cell Counting Kit‑8 and BrdU assays, cell migration was assessed by performing the wound healing assay, cell invasion was detected by performing the Transwell assay, and VEGFR/AKT signaling pathway‑related protein expression levels were measured via western blotting. The results demonstrated that OGN expression was significantly downregulated in patients with AD compared with healthy controls. Compared with the si‑negative control (NC) group, OGN knockdown promoted RASMC proliferation and migration. Compared with the si‑NC group, OGN knockdown also significantly enhanced the phosphorylation of the downstream signaling molecules of VEGFR, including AKT and ERK1/2, in VEGF‑stimulated RASMCs. Collectively, the present study indicated that OGN knockdown facilitated RASMC proliferation and migration by activating AKT and ERK1/2 signaling. Therefore, OGN may serve as a novel therapeutic target for AD.
细胞外基质（ECM）蛋白在主动脉夹层（AD）的发病机制中起主要作用。本研究旨在探讨 ECM 蛋白聚糖骨桥蛋白（OGN）对 AD 的影响及其潜在机制。收集 20 例 AD 患者的胸主动脉组织和 5 例行冠状动脉旁路移植术的健康胸主动脉组织，检测 OGN 表达水平。在大鼠主动脉平滑肌细胞中敲低 OGN 后，通过 Cell Counting Kit-8 和 BrdU 检测细胞增殖，通过划痕愈合实验评估细胞迁移，通过 Transwell 检测细胞侵袭，通过 Western blot 检测 VEGFR/AKT 信号通路相关蛋白表达水平。结果表明，AD 患者的 OGN 表达明显下调。与阴性对照 si-NC 组相比，OGN 敲低促进 RASMC 增殖和迁移。与 si-NC 组相比，OGN 敲低还显著增强了 VEGFR 下游信号分子 AKT 和 ERK1/2 的磷酸化，在 VEGF 刺激的 RASMC 中。综上所述，本研究表明，OGN 敲低通过激活 AKT 和 ERK1/2 信号通路促进 RASMC 的增殖和迁移。因此，OGN 可能成为 AD 的一种新的治疗靶点。
