Hainan General Hospital, Haikou, Hainan, China.
The Affiliated Hainan Hospital of Hainan Medical University, Haikou, Hainan, China.
Cell Prolif. 2023 Nov;56(11):e13491. doi: 10.1111/cpr.13491. Epub 2023 May 8.
Oral submucous fibrosis (OSF) has a high incidence in Asia countries, but its underlying molecular mechanism was not exploited completely. In this research, we investigated the expression of the phosphatidyl inositol 3-kinase (Pi3k)/protein kinase B (Akt) pathway and vascular endothelial growth factor (VEGF) in oral submucosal fibrosis, explore the correlation between the Pi3k/Akt pathway and VEGF, and identify the mechanisms involved in OSF. The pathological changes and fibrosis stages of OSF tissues (n = 30, 10 each of early, moderate and advanced OSF) were determined using Haematoxylin-eosin staining (HE) and Masson staining, respectively. Collagen type I (Col-I), Pi3k, Akt, VEGF, TGF-β and p-Akt expression was detected using immunohistochemistry, qPCR and WB. The correlation between Pi3k, Akt and VEGF was analysed. Col-I expression increased as OSF progressed. However, their expression was downregulated in normal and moderate to advanced OSF tissues. VEGF expression positively correlated with Pi3k and Akt expression. VEGF expression correlated positively and negatively with the Pi3k inhibitor, LY294002 below and above a concentration of 10 μM, respectively. VEGF expression correlated positively with the Pi3k/Ak activator, IGF-1. Due to the synergistic effect between Pi3k/Akt pathway and VEGF on OSF lesions and fibrosis process, targeted Pi3k/Akt pathway regulation can induce VEGF expression and improve ischemia, ultimately treating OSF.
口腔黏膜下纤维性变(OSF)在亚洲国家发病率较高,但其潜在的分子机制尚未完全阐明。在这项研究中,我们研究了磷脂酰肌醇 3-激酶(PI3K)/蛋白激酶 B(Akt)通路和血管内皮生长因子(VEGF)在口腔黏膜下纤维性变中的表达,探讨了 PI3k/Akt 通路与 VEGF 之间的相关性,并确定了 OSF 涉及的机制。采用苏木精-伊红染色(HE)和 Masson 染色分别确定 OSF 组织(n=30,早期、中期和晚期 OSF 各 10 例)的病理变化和纤维化分期。采用免疫组织化学、qPCR 和 WB 检测胶原 I(Col-I)、PI3k、Akt、VEGF、TGF-β和 p-Akt 的表达。分析了 Pi3k、Akt 和 VEGF 之间的相关性。随着 OSF 的进展,Col-I 的表达增加。然而,在正常和中晚期 OSF 组织中,其表达下调。VEGF 的表达与 Pi3k 和 Akt 的表达呈正相关。VEGF 的表达与 Pi3k 抑制剂 LY294002 的浓度低于 10 μM 时呈正相关,高于 10 μM 时呈负相关。VEGF 的表达与 Pi3k/Akt 激活剂 IGF-1 呈正相关。由于 Pi3k/Akt 通路和 VEGF 对 OSF 病变和纤维化过程的协同作用,靶向 Pi3k/Akt 通路调节可诱导 VEGF 表达,改善缺血,最终治疗 OSF。