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

Acta Odontol Scand. 2014 Oct;72(7):549-56. doi: 10.3109/00016357.2013.879995. Epub 2014 Jan 29.

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.

Keywords: Sjögren's Syndrome; aquaporins; calcium signaling; cell volume regulation; saliva.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aquaporin 1 / analysis
  • Aquaporin 3 / analysis
  • Aquaporin 5 / analysis
  • Aquaporins / analysis
  • Calcium Signaling / drug effects
  • Calcium Signaling / physiology*
  • Carbachol / pharmacology
  • Cell Size
  • Cholinergic Agonists / pharmacology
  • Cohort Studies
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Saliva / chemistry
  • Saliva / metabolism
  • Salivary Glands / drug effects
  • Salivary Glands / metabolism
  • Salivary Glands / pathology*
  • Single-Blind Method
  • Sjogren's Syndrome / pathology
  • Sjogren's Syndrome / physiopathology*

Substances

  • AQP3 protein, human
  • AQP5 protein, human
  • Aquaporin 5
  • Aquaporins
  • Cholinergic Agonists
  • Aquaporin 1
  • Aquaporin 3
  • Carbachol