P2Y[subscript 2] nucleotide receptor up-regulation and function in submandibular gland epithelium

Abstract

Sjögren's syndrome (SS) is an autoimmune disease that specifically targets exocrine glands, including salivary glands, and results in an impairment of secretory function. P2Y₂ nucleotide receptors for extracellular ATP and UTP are up-regulated in response to stress or injury in a variety of tissues including submandibular glands (SMGs). Therefore, our objective was to assess whether P2Y₂ receptor expression is up-regulated in SMGs of the NOD.B10 mouse model of SS, and to determine the function of P2Y₂Rs in salivary gland tissue. Our data indicate that P2Y₂Rs are up-regulated in SMGs of the NOD.B10 mice, and this up-regulation increases as the disease progresses. Moreover, data obtained using a human submandibular gland cell line, demonstrate that P2Y₂Rs activate a signaling pathway leading to gene transcription via at least two distinct mechanisms. These findings suggest that regulation of P2Y₂Rs is likely to be an important therapeutic target for various diseases.