Research Paper|Volume 11, Issue 19|pp 8254—8269

Soluble klotho regulates the function of salivary glands by activating KLF4 pathways

Nguyen Chi Tai¹, Soo-A Kim², Sang-Gun Ahn¹

¹Department of Pathology, School of Dentistry, Chosun University, Gwangju 61452, Republic of Korea
²Department of Biochemistry, School of Oriental Medicine, Dongguk University, Gyeongju 38066, Republic of Korea

Received: April 22, 2019Accepted: September 21, 2019Published: October 2, 2019

Copyright © 2019 Tai et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

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 (α-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.