Department of Biomedical Sciences, School of Dental Medicine, University of Nevada Las Vegas, Las Vegas, NV, USA.
School of Dental Medicine, University of Puerto Rico, San Juan, Puerto Rico.
Adv Exp Med Biol. 2019;1197:143-163. doi: 10.1007/978-3-030-28524-1_11.
Epithelial cells and functions of the epithelium are critical to the health of the oral cavity. We used a nonhuman primate model to profile the transcriptome of gingival tissues in health across the lifespan and hypothesized that in older animals, epithelial-related transcriptome patterns would reflect epithelial cells that are aggressively responsive to the surrounding environment and less able to modulate and resolve the noxious challenge from the bacteria. Rhesus monkeys (n = 34) with a healthy periodontium were distributed into four groups: ≤3 years (young), 3-7 years (adolescent), 12-16 years (adult), and 18-23 years (aged), and a buccal gingival sample from the premolar/molar region of each animal was obtained. RNA was subjected to a microarray analysis (GeneChip Rhesus Macaque Genome Array, Affymetrix), and 336 genes examined that are linked to epithelium and epithelial cell functions categorized into 9 broad functional groups: extracellular matrix and cell structure; extracellular matrix remodeling enzymes; cell adhesion molecules, cytoskeleton regulation; inflammatory response; growth factors; kinases/cell signaling; cell surface receptors; junction associated molecules; autophagy/apoptosis; antimicrobial peptides; and transcription factors. Total of 255 genes displayed a normalized signal >100, and differences across the age groups were observed primarily in extracellular matrix and cell structure, cell adhesion molecules, and cell surface receptor gene categories with elevations in the aged tissues. Keratins 2, 5, 6B, 13, 16, 17 were all significantly increased in healthy-aged tissues versus adults, and keratins 1 and 2 were significantly decreased in young animals. Approximately 15 integrins are highly expressed in the gingival tissues across the age groups with only ITGA8, ITGAM (CD11b), and ITGB2 significantly increased in the aged tissues. Little impact of aging on desmosomal/hemidesmosomal genes was noted. These results suggest that healthy gingival aging has a relatively limited impact on the broader functions of the epithelium and epithelial cells, with some effects on genes for extracellular matrix and cell adhesion molecules (e.g., integrins). Thus, while there is a substantial impact of aging on immune system targets even in healthy gingiva, it appears that the epithelial barrier remains reasonably molecularly intact in this model system.
上皮细胞及其功能对口腔健康至关重要。我们使用非人类灵长类动物模型来描绘整个生命周期中牙龈组织的转录组图谱，并假设在老年动物中，与上皮相关的转录组模式将反映出积极响应周围环境的上皮细胞，而这些细胞的调节和解决来自细菌的有害挑战的能力较弱。具有健康牙周组织的恒河猴（n=34）分为四组：≤3 岁（年轻）、3-7 岁（青少年）、12-16 岁（成年）和 18-23 岁（老年），并从每个动物的前磨牙/磨牙区获得颊侧牙龈样本。RNA 进行微阵列分析（GeneChip 恒河猴基因组阵列，Affymetrix），并检查了 336 个与上皮和上皮细胞功能相关的基因，这些基因分为 9 个广泛的功能组：细胞外基质和细胞结构；细胞外基质重塑酶；细胞黏附分子、细胞骨架调节；炎症反应；生长因子；激酶/细胞信号；细胞表面受体；连接相关分子；自噬/凋亡；抗菌肽；和转录因子。共有 255 个基因的归一化信号>100，并且在年龄组之间观察到的差异主要在细胞外基质和细胞结构、细胞黏附分子和细胞表面受体基因类别中，老年组织中这些基因的表达升高。角蛋白 2、5、6B、13、16、17 在健康老年组织中的表达均明显高于成年组织，而在年轻动物中角蛋白 1 和 2 的表达明显降低。在整个年龄组中，大约有 15 种整合素在牙龈组织中高度表达，只有 ITGA8、ITGAM（CD11b）和 ITGB2 在老年组织中显著增加。衰老对桥粒/半桥粒基因的影响很小。这些结果表明，健康牙龈的衰老对上皮和上皮细胞的更广泛功能的影响相对有限，而对细胞外基质和细胞黏附分子（例如整合素）的基因有一些影响。因此，即使在健康的牙龈中，衰老对免疫系统靶点也有很大的影响，但在这个模型系统中，上皮屏障似乎在分子上仍然相当完整。
