Expression of PINK1 and Parkin in human apical periodontitis
Expression of PINK1 and Parkin in human apical periodontitis
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PINK1和Parkin在人根尖周炎中的表达
DOI：
10.1111/iej.13760
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发表时间：
2022-05-25
影响因子：
5
通讯作者：
Peng, Bin
中科院分区：
文献类型：
--
作者：
Liu, Bingqian;Zhang, Jie;Peng, Bin
目的PTEN诱导的蛋白激酶1（PINK 1）和Parkin E3泛素蛋白连接酶（Parkin）在健康和疾病的免疫和炎症调节中起着关键作用。PINK 1和Parkin已被证实通过影响线粒体吞噬相关的成骨细胞凋亡参与根尖牙周炎的进展;然而，PINK 1和Parkin在根尖牙周炎中最重要的细胞之一巨噬细胞中的表达仍然未知。本研究旨在探讨PINK 1和Parkin在人类根尖周炎病变中的表达及其在巨噬细胞中的可能定位。方法选取根尖周肉芽肿（PGs，n = 12）、根尖囊肿（RCs，n = 11）和正常牙龈组织（n = 14）共37例。HE染色观察病灶内炎性浸润情况，免疫组化检测PINK 1和Parkin蛋白的表达。应用免疫荧光双标技术检测微管相关蛋白1轻链3（micropubule-associated protein 1 light chain 3，LC 3）和TOMM 20在人根尖周炎病变组织中的共定位，以及PINK 1和Parkin在人根尖周炎病变组织中的共定位。应用透射电镜观察了人根尖周炎病变组织中线粒体的超微结构。资料以单因子变异数分析，并以Student-Newman-Keul检验及Mann-Whitney检验。p <0.05被认为具有统计学显著性。结果PINK 1和Parkin蛋白在人根尖周炎病变组织中的表达显著高于正常牙龈组织（p < .0001），但在PGs和RCs中的表达无显著性差异（p > .05）。根尖周炎组织中LC 3的表达明显增强，LC 3-TOMM 20双阳性细胞增多。PINK 1、Parkin和LC 3与CD 68的双标记分析表明，巨噬细胞的线粒体自噬可能在人类根尖周炎的进展中存在。透射电镜形态学分析结果显示，根尖病变的巨噬细胞样细胞中出现双膜线粒体吞噬体和空泡化线粒体。结论PINK 1和Parkin蛋白在根尖周炎中有较高的表达。
Aim PTEN-induced putative kinase 1 (PINK1) and Parkin E3 ubiquitin-protein ligase (Parkin) are critical for immune and inflammatory regulation in health and disease. PINK1 and Parkin have been confirmed to be involved in the progression of apical periodontitis by affecting mitophagy-related osteoblast apoptosis; however, the expression of PINK1 and Parkin in macrophages, one of the most important cells in apical periodontitis, remains unknown. This study aimed to investigate the expression of PINK1 and Parkin in human apical periodontitis lesions, as well as their possible localization in macrophages. Methodology Thirty-seven human periapical tissues, including periapical granulomas (PGs, n = 12), radicular cysts (RCs, n = 11) and healthy gingival tissues (n = 14) were examined. The inflammatory infiltrates of lesions were evaluated by haematoxylin staining, and the expression of PINK1 and Parkin was detected by immunohistochemistry. Double immunofluorescence was used to explore the colocalization of microtubule-associated protein 1 light chain 3 (LC3) and TOMM20, as well as the localization of PINK1 and Parkin, in macrophages of human apical periodontitis lesions. The ultrastructural morphology of mitochondria in human apical periodontitis lesions was visualized by transmission electron microscopy (TEM). Data were analysed by one-way anova with Student-Newman-Keul's test and the Mann-Whitney test. p < .05 was considered statistically significant. Results Immunohistochemistry demonstrated a significantly higher expression of PINK1 and Parkin proteins in human apical periodontitis lesions than in healthy gingival tissues (p < .0001), but no significant difference was demonstrated between PGs and RCs (p > .05). The higher expression of LC3 and the presence of more LC3-TOMM20 double-positive cells were also observed in human apical periodontitis. Double-labelling analysis of PINK1, Parkin and LC3 with CD68 indicated that macrophage mitophagy might be present in the progression of human apical periodontitis. Finally, the results of TEM morphological analysis revealed the appearance of double-membraned mitophagosomes and vacuolated mitochondria in macrophage-like cells of apical periodontitis lesions. Conclusions Our findings indicated that PINK1 and Parkin proteins were highly expressed in clinical apical periodontitis lesions.