Sjogren’s syndrome induces salivary and lacrimal hyposecretion, which leads to reduced quality of life. Although many studies have been conducted from the perspective of inflammation, the development of a causal treatment has not been achieved yet. We previously investigated the cause from the perspective of non-inflammation, and identified arginase 1 as a novel non-inflammatory regulator of exocrine function. However, the mechanism of arginase 1 regulating the function remains unknown, so we aimed to elucidate the mechanism.
We first confirmed the expression of arginase 1 in both salivary and lacrimal glands from BALB/c mice. Arginase 1 inhibitor, CB-1158, reduced the pilocarpine-induced saliva and tear secretion in vivo. The metabolome analysis of lacrimal glands revealed the altered concentration of amino acids related to energy metabolism. Furthermore, in an ex vivo perfusion system in which submandibular glands removed from the CB-1158-treated mice were cannulated with arteries, the saliva flow rate immediately after stimulation was unchanged compared to the control group but then decreased. We did not observe the saliva decrease in ex vivo experiments with perfusion of CB-1158 itself. These results indicated that arginase 1 might regulate paracellular fluid secretion via energy metabolism.