Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Department of Periodontics, School of Stomatology, Tongji University, Shanghai, China.
Dental Diseases Prevention & Treatment Center of Jiading District, Shanghai, China.
J Periodontal Res. 2021 Apr;56(2):265-274. doi: 10.1111/jre.12812. Epub 2020 Dec 29.
The involvement of lysosomal integral membrane protein 2 (LIMP2) in cholesterol transport and formation of foam cells under the infection of Porphyromonas gingivalis (P. gingivalis) is yet to be elucidated. The current study verified the role and explored the mechanism of LIMP2 in promoting foam cell formation by P. gingivalis.
An association between periodontitis and atherosclerosis (AS) has been established. P. gingivalis is a key pathogen of periodontitis that promotes foam cell formation by regulating activities of CD36 scavenger receptors expressed on the macrophages. LIMP2, a member of CD36 superfamily, is involved in cholesterol efflux. However, whether LIMP2 is involved in the formation of foam cells promoted by P. gingivalis remains unclear.
The formation of foam cells was examined by Oil Red O staining. The knockdown of limp2 was identified by qRT-PCR. The accumulation of cholesterol was monitored by Cholesterol Assay Kit. The location of P. gingivalis was visualized by confocal microscopy. Cathepsin L activity was monitored with Magic Red Cathepsin L Assay Kit. The key genes and pathways in P. gingivalis-infected macrophages were explored by RNA sequencing. The protein level was investigated by Western blotting.
Porphyromonas gingivalis increases foam cells formation and upregulates the expression of LIMP2 in foam cells. The knockdown of limp2 decreases the number of foam cells and increases cholesterol export, which is related to lysosomal functions. In addition, the interaction between LIMP2 and caveolin-1(CAV1) might contribute to this process, and NF-κB and JNK activity is required for increased expression of P. gingivalis-induced LIMP2.
This study suggested that LIMP2 is involved in the foam cells formation facilitated by P. gingivalis, which favors a close connection between periodontitis and atherosclerosis (AS).
牙龈卟啉单胞菌（P. gingivalis）感染下溶酶体整合膜蛋白 2（LIMP2）在胆固醇转运和泡沫细胞形成中的作用尚不清楚。本研究验证了 LIMP2 在促进牙龈卟啉单胞菌诱导泡沫细胞形成中的作用，并探讨了其机制。
牙周炎与动脉粥样硬化（AS）之间存在关联。P. gingivalis 是牙周炎的关键病原体，通过调节巨噬细胞表面表达的 CD36 清道夫受体的活性来促进泡沫细胞形成。LIMP2 是 CD36 超家族的成员，参与胆固醇外排。然而，LIMP2 是否参与 P. gingivalis 诱导的泡沫细胞形成尚不清楚。
通过油红 O 染色检测泡沫细胞的形成。qRT-PCR 鉴定 limp2 的敲低。用胆固醇测定试剂盒监测胆固醇的积累。通过共聚焦显微镜观察 P. gingivalis 的位置。用 Magic Red Cathepsin L 检测试剂盒监测组织蛋白酶 L 活性。通过 RNA 测序探索牙龈卟啉单胞菌感染的巨噬细胞中的关键基因和通路。用 Western blot 检测蛋白水平。
牙龈卟啉单胞菌增加泡沫细胞的形成，并上调泡沫细胞中 LIMP2 的表达。limp2 的敲低减少了泡沫细胞的数量，并增加了胆固醇的外排，这与溶酶体功能有关。此外，LIMP2 与 caveolin-1（CAV1）的相互作用可能有助于这一过程，NF-κB 和 JNK 活性是牙龈卟啉单胞菌诱导 LIMP2 表达增加所必需的。
本研究表明，LIMP2 参与了牙龈卟啉单胞菌促进的泡沫细胞形成，这有利于牙周炎和动脉粥样硬化（AS）之间的密切联系。
