First Author | Tai NC | Year | 2019 |
Journal | Aging (Albany NY) | Volume | 11 |
Issue | 19 | Pages | 8254-8269 |
PubMed ID | 31581134 | Mgi Jnum | J:322725 |
Mgi Id | MGI:7259922 | Doi | 10.18632/aging.102318 |
Citation | Tai NC, et al. (2019) Soluble klotho regulates the function of salivary glands by activating KLF4 pathways. Aging (Albany NY) 11(19):8254-8269 |
abstractText | The dysfunction of salivary glands commonly induces dry mouth, infections, and dental caries caused by a lack of saliva. This study was performed to determine the genetic and functional changes in salivary glands using a klotho (-/-) mouse model. Here, we confirmed the attenuation of KLF4 expression in the salivary glands of klotho (-/-) mice. Soluble klotho overexpression induced KLF4 transcription and KLF4-mediated signaling pathways, including mTOR, AMPK, and SOD1/2. Silencing klotho via siRNA significantly down-regulated KLF4 expression. Additionally, we monitored the function of salivary glands and soluble klotho and/or KLF4 responses and demonstrated that soluble klotho increased the expression of KLF4 and markers of salivary gland function (alpha-amylase, ZO-1, and Aqua5) in primary cultured salivary gland cells from wild type and klotho (-/-) mice. In a 3D culture system, cell sphere aggregates were observed in soluble klotho- or KLF4-expressing cells and exhibited higher expression levels of salivary gland function-related proteins than those in nontransfected cells. These results suggest that activation of the klotho-mediated KLF4 signaling pathway contributes to potentiating the function of salivary glands. |