Calcium signaling and cell volume regulation are altered in Sjögren's Syndrome

Abstract

Objective. Sjögren's Syndrome (SS) is a chronic autoimmune disease, leading to deficient secretion from salivary and lacrimal glands. Saliva production is normally increased by cholinergic innervation, giving rise to intracellular calcium signaling and water transport through water channels (aquaporins, AQPs). The aim of this study was to investigate possible pathophysiological changes in cell volume regulation, AQP expression and localization, and intracellular calcium signaling in glandular cells from SS patients compared to controls. Materials and methods. A total of 35 SS patients and 41 non-SS controls were included. Real time qPCR was combined with immunohistochemistry to analyze the mRNA expression and cellular distribution of AQP1, 3 and 5. Cell volume regulation and intracellular calcium signaling were examined in fresh acinar cells. Results. We show for the first time a reduced mRNA expression of AQP1 and 5 in SS compared to controls, accompanied by a decrease in staining intensity of AQP1, 3 and 5 in areas adjacent to local lymphocytic infiltration. Furthermore, we observed that the SS cells' capacity for volume regulation was abnormal. Similarly, the calcium response after parasympathetic agonist (carbachol) stimulation was markedly decreased in SS cells. Conclusions. It is concluded that mRNA expression of AQP1 and 5, protein distribution of AQP1, 3 and 5, glandular cell volume regulation and intracellular calcium signaling are all altered in SS, pointing to possible pathophysiological mechanisms in SS.

Key Words::

• aquaporins
• calcium signaling
• cell volume regulation
• saliva
• Sjögren's Syndrome

Acknowledgments

We are grateful to Professor Kathrine Skarstein for helpful discussions on etiological and histological aspects of SS, to Ann-Kristin Ruus, MSc and Olav Schreurs for technical assistance and to Professor Leiv Sandvik for statistical assistance and manuscript revisions. We are also very grateful to Professor Emeritus Haakon B. Benestad for insightful inputs during manuscript revision. We thank the faculty and staff at the Department of Oral Surgery and Oral Medicine for always being helpful and caring for the patients. Lastly, we thank the patients for participating in our research—without them this work could not have been carried out. The work was supported by the University of Oslo, Norway.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.