Department of Oral and Maxillofacial Pathology, College of Dentistry, Wonkwang University, Daejeon, Republic of Korea.
Department of Biochemistry, College of Oriental Medicine, Dongguk University, Gyeongju, Republic of Korea.
J Cell Physiol. 2018 Apr;233(4):3282-3294. doi: 10.1002/jcp.26172. Epub 2017 Sep 28.
Salivary dysfunction commonly occurs in many older adults and is considered a physiological phenomenon. However, the genetic changes in salivary glands during aging have not been characterized. The present study analyzed the gene expression profile in salivary glands from accelerated aging klotho deficient mice (klotho-/-, 4 weeks old). Microarray analysis showed that 195 genes were differentially expressed (z-score > 2 in two independent arrays) in klotho null mice compared to wild-type mice. Importantly, alpha2-Na /K -ATPase (Atp1a2), Ca -ATPase (Atp2a1), epidermal growth factor (EGF), and nerve growth factor (NGF), which have been suggested to be regulators of submandibular salivary gland function, were significantly decreased. When a network was constructed from the differentially expressed genes, proliferator-activated receptor-γ (PPAR γ), which regulates energy homeostasis and insulin sensitivity, was located at the core of the network. In addition, the expression of genes proposed to regulate various PPAR γ-related cellular pathways, such as Klk1b26, Egfbp2, Cox8b, Gpx3, Fabp3, EGF, and NGFβ, was altered in the submandibular salivary glands of klotho-/- mice. Our results may provide clues for the identification of novel genes involved in salivary gland dysfunction. Further characterization of these differentially expressed genes will be useful in elucidating the genetic basis of aging-related changes in the submandibular salivary gland.
唾液功能障碍常见于许多老年人，被认为是一种生理现象。然而，衰老过程中唾液腺的遗传变化尚未得到阐明。本研究分析了加速衰老 klotho 缺陷小鼠（klotho-/-，4 周龄）唾液腺的基因表达谱。微阵列分析显示，klotho 缺失小鼠与野生型小鼠相比，有 195 个基因表达存在差异（两个独立数组中的 z 分数>2）。重要的是，α2-Na /K -ATPase（Atp1a2）、Ca -ATPase（Atp2a1）、表皮生长因子（EGF）和神经生长因子（NGF）的表达显著降低，这些因子被认为是调节颌下唾液腺功能的调节剂。当从差异表达基因构建网络时，调节能量稳态和胰岛素敏感性的过氧化物酶体增殖物激活受体-γ（PPAR γ）位于网络的核心。此外，klotho-/-小鼠颌下唾液腺中，一些被提议调节各种与 PPAR γ 相关的细胞途径的基因，如 Klk1b26、Egfbp2、Cox8b、Gpx3、Fabp3、EGF 和 NGFβ 的表达也发生了改变。我们的研究结果可能为鉴定参与唾液腺功能障碍的新基因提供线索。这些差异表达基因的进一步特征分析将有助于阐明颌下唾液腺与衰老相关变化的遗传基础。
