槟榔碱诱导的自噬在口腔黏膜下纤维性变血管生成中的作用。
Role of autophagy induced by arecoline in angiogenesis of oral submucous fibrosis.
机构信息
Centre of Stomatology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
School of Stomatology, Changsha Medical University, Changsha, Hunan, China.
出版信息
Arch Oral Biol. 2019 Jun;102:7-15. doi: 10.1016/j.archoralbio.2019.03.021. Epub 2019 Mar 28.
OBJECTIVES
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.
METHODS
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.
RESULTS
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.
CONCLUSIONS
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.
目的
检测蛋白轻链 3（LC3）和 p62-SQSTM1（p62）在口腔黏膜下纤维化（OSF）固有层中的表达，并确定自噬与 OSF 的关联。研究自噬在人脐静脉内皮细胞（HUVEC）血管生成中的作用，并评估这种作用是否是由槟榔碱诱导的。
方法
通过免疫组织化学（IHC）检测 OSF 组织中 LC3 和 p62 的表达。透射电子显微镜（TEM）和 Western blot 用于研究 HUVEC 中自噬的表达。使用 Matrigel 测定法研究自噬在 HUVEC 血管生成中的作用。
结果
1：LC3 在 OSF 样本中表达上调。相比之下，p62 在 OSF 的早期和中期阶段下调，但在晚期阶段上调。2：用槟榔碱处理的 HUVECs 显示自噬体、LC3 表达增加，p62 表达减少，当与氯喹（CQ）共同处理时，这是一种特定的自噬抑制剂，呈现相反的趋势。3：自噬抑制 HUVECs 的血管生成。
结论
我们的发现表明，槟榔碱诱导 HUVEC 中的自噬。高水平的自噬可能会降低细胞活力并抑制 HUVECs 的血管生成，从而可能促进 OSF 的发展。
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