Department of Biomedical Sciences, School of Dental Medicine, University of Nevada Las Vegas, NV, USA.
Center for Oral Health Research, University of Kentucky, Lexington, KY, USA.
J Periodontal Res. 2021 Jan;56(1):34-45. doi: 10.1111/jre.12789. Epub 2020 Aug 9.
We hypothesized that autophagy-related genes will be differentially expressed in periodontitis, suggesting an impaired gingival autophagic response associated with disease.
Autophagy is a cellular physiologic mechanism to maintain tissue homeostasis, while deficient autophagic responses increase inflammation and susceptibility to infection.
Rhesus monkeys [<3 years to 23 years of age (n = 34)] were examined for periodontal health and naturally occurring periodontitis. Gingival tissues samples were obtained from healthy or diseased sites, total RNA was isolated, and the Rhesus Gene Chip 1.0 ST (Affymetrix) was used for gene expression analysis of 150 autophagy-related genes.
Comparison of expression levels with adult healthy tissues demonstrated a rather limited number of individual genes that were significantly different across the age-groups. In contrast, with periodontitis in the adults and aged animals, about 15% of the genes were significantly increased or decreased. The differences were reflected in the mTOR complex (5/12), ULK1/ATG1 complex (5/9), PI3K complex (5/21), ATG9 complex (2/7), ATG12 conjugation/LC3 lipidation (7/22), and lysosome fusion/vesicle degradation [LF/VD (5/10)] activities within the broader autophagic pathway. The genes most greatly altered in gingival tissues of naturally occurring periodontitis were identified in the ATG12 and LF/VD pathways that approximated 50% of the genes in each of those categories. While healthy gingival aging did not appear to reflect altered autophagy gene expression, substantial differences were noted with periodontitis irrespective of the age of the animals. Future studies into the role of autophagy in periodontitis and could offer potential new therapeutic strategies to prevent and/or treat periodontal disease.
我们假设自噬相关基因在牙周炎中会有差异表达，提示与疾病相关的牙龈自噬反应受损。
自噬是一种维持组织内稳态的细胞生理机制，而自噬反应不足会增加炎症和感染易感性。
对<3 至 23 岁（n=34）的恒河猴进行牙周健康和自然发生的牙周炎检查。从健康或患病部位获取牙龈组织样本，分离总 RNA，并使用恒河猴基因芯片 1.0 ST（Affymetrix）对 150 个自噬相关基因的表达进行分析。
与成年健康组织的表达水平相比，各年龄段之间存在显著差异的单个基因数量相当有限。相比之下，在成年和老年动物的牙周炎中，约 15%的基因显著增加或减少。这些差异反映在 mTOR 复合物（5/12）、ULK1/ATG1 复合物（5/9）、PI3K 复合物（5/21）、ATG9 复合物（2/7）、ATG12 连接/LC3 脂质化（7/22）和溶酶体融合/囊泡降解[LF/VD（5/10）]活性等更广泛的自噬途径中。在自然发生的牙周炎的牙龈组织中改变最大的基因被鉴定为 ATG12 和 LF/VD 途径，每个途径中的基因约占 50%。虽然健康牙龈的衰老似乎不会反映自噬基因表达的改变，但无论动物年龄大小，牙周炎都会出现明显差异。未来对自噬在牙周炎中的作用的研究可能为预防和/或治疗牙周病提供潜在的新治疗策略。
