Role of autophagy induced by arecoline in angiogenesis of oral submucous fibrosis

• Published in: Archives of oral biology 2019-06, Vol.102, p.7-15
• Main Authors: Dai, Zhuo, Zhu, Bingyu, Yu, Huiqiao, Jian, Xinchun, Peng, Jieying, Fang, Changyun, Wu, Yingfang
• Format: Article
• Language: English
• Subjects: Angiogenesis; Arecoline; Autophagy; Cell Survival; Dentistry; Human Umbilical Vein Endothelial Cells; Humans; LC3; Oral Submucous Fibrosis; p62
• ISSN: 0003-9969; 1879-1506
• DOI: 10.1016/j.archoralbio.2019.03.021

•Autophagy in HUVECs could be induced by arecoline both in vivo and in vitro.•Oral submucous fibrosis samples showed a higher level of autophagy compared with normal samples.•A proper level of autophagy played a protective role in HUVECs via promoting angiogenesis.•Arecoline could induce uncontrolled autophagy in HUVECs, which led to abnormal endothelial cell function and inhibited angiopoiesis.•Autophagy activation mediated by arecoline might be one pathogenic mechanism in OSF by regulating angiogenesis. To detect the expression of protein light chain 3 (LC3) and p62-SQSTM1 (p62) in the lamina propria of oral submucous fibrosis (OSF) and to determine the association of autophagy with OSF. To investigate the role of autophagy in angiogenesis of human umbilical vein endothelial cells (HUVECs) and to assess whether this effect was induced by arecoline. LC3 and p62 expression was detected in OSF tissue through immunohistochemistry (IHC). Transmission electron microscopy (TEM) and Western blot were used to investigate the expression of autophagy in HUVECs. The role of autophagy in angiogenesis in HUVECs was investigated using the Matrigel assay. 1: LC3 expression was upregulated in OSF samples. In contrast, p62 was downregulated in early and intermediate stages but upregulated in advanced stages of OSF. 2: HUVECs treated with arecoline exhibited increased autophagosomes, LC3 expression and reduced p62 expression, when co-treated with chloroquine (CQ), which is a specific autophagy inhibitor, revealed the opposite trend. 3: Autophagy inhibited angiogenesis in HUVECs. Our findings suggest that arecoline induces autophagy in HUVECs. The high level of autophagy could reduce cell viability and inhibit angiogenesis in HUVECs, potentially promoting the development of OSF.