Brain Korea 21 Project for Biomedical Science, Guro Hospital, Korea University, Seoul 152-703, South Korea.
Exp Biol Med (Maywood). 2012 Jun;237(6):663-9. doi: 10.1258/ebm.2012.011342. Epub 2012 Jun 22.
Nasal polyps are associated with chronic inflammation of the sinonasal mucosa and are involved in myofibroblast differentiation and extracellular matrix (ECM) accumulation. Ginsenoside Rg1, a compound derived from Panax ginseng, shows antifibrotic and anticancer effects. However, the molecular effects of Rg1 on myofibroblast differentiation and ECM production remain unknown. The aims of this study were to investigate the effect of Rg1 on transforming growth factor (TGF)-β1-induced myofibroblast differentiation and ECM production and to determine the molecular mechanism of Rg1 in nasal polyp-derived fibroblasts (NPDFs). NPDFs were isolated from nasal polyps of seven patients who had chronic rhinosinusitis with nasal polyp. NPDFs were exposed to TGF-β1 with or without Rg1. Expression levels of α-smooth muscle actin (SMA), fibronectin and collagen type Iα1 were determined by reverse transcription polymerase chain reaction, Western blot and immunofluorescent staining. TGF-β1 signaling molecules, including Smad2/3, extracellular signal-regulated protein kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 were analyzed by Western blotting. Transcription factors involved with TGF-β1 signaling, nuclear factor (NF)-κB and activator protein 1 (AP-1) were also assessed by Western blot. The cytotoxic effect of Rg1 was measured by an established viability assay. The mRNA and protein expression levels of α-SMA, fibronectin and collagen type Iα1 were increased in TGF-β1-induced NPDFs. Rg1 inhibited these effects. The inhibitory molecular mechanism of Rg1 was involved in the ERK pathway. Rg1 inhibited the transcription factor activation of AP-1. Rg1 itself was not cytotoxic. The ginsenoside Rg1 has inhibitory effects on myofibroblast differentiation and ECM production. The inhibitory mechanism of Rg1 is involved with the ERK and AP-1 signaling pathways. Rg1 may be useful as an inhibitor of ECM deposition, and has potential to be used as a novel treatment option for nasal polyps.
鼻息肉与鼻黏膜的慢性炎症有关，参与成肌纤维细胞分化和细胞外基质（ECM）的积累。人参皂苷 Rg1 是从人参中提取的一种化合物，具有抗纤维化和抗癌作用。然而，Rg1 对成肌纤维细胞分化和 ECM 产生的分子作用尚不清楚。本研究旨在探讨 Rg1 对转化生长因子（TGF）-β1 诱导的成肌纤维细胞分化和 ECM 产生的影响，并确定 Rg1 在鼻息肉衍生成纤维细胞（NPDFs）中的分子机制。NPDFs 从 7 名患有慢性鼻-鼻窦炎伴鼻息肉的患者的鼻息肉中分离出来。用或不用 Rg1 处理 NPDFs 使其暴露于 TGF-β1 中。通过逆转录聚合酶链反应、Western blot 和免疫荧光染色测定α-平滑肌肌动蛋白（SMA）、纤维连接蛋白和胶原 Iα1 的表达水平。通过 Western blot 分析 TGF-β1 信号分子，包括 Smad2/3、细胞外信号调节激酶（ERK）、c-Jun N 端激酶（JNK）和 p38。还通过 Western blot 评估与 TGF-β1 信号相关的转录因子核因子（NF）-κB 和激活蛋白 1（AP-1）。通过已建立的活力测定法测量 Rg1 的细胞毒性作用。TGF-β1 诱导的 NPDFs 中α-SMA、纤维连接蛋白和胶原 Iα1 的 mRNA 和蛋白表达水平增加，Rg1 抑制了这些作用。Rg1 的抑制作用的分子机制涉及 ERK 途径。Rg1 抑制了 AP-1 的转录因子激活。Rg1 本身没有细胞毒性。人参皂苷 Rg1 对成肌纤维细胞分化和 ECM 产生具有抑制作用。Rg1 的抑制机制涉及 ERK 和 AP-1 信号通路。Rg1 可能作为 ECM 沉积的抑制剂有用，并具有作为鼻息肉新的治疗选择的潜力。
