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


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.
Department of Oral Surgery and Oral Medicine.
Tone Berge
TB
Enger
Marit Høyberg
MH
Aure
Janicke Liaaen
JL
Jensen
Hilde Kanli
HK
Galtung
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051398:Aquaporin 1 / Q000032:analysis; D051400:Aquaporin 3 / Q000032:analysis; D051402:Aquaporin 5 / Q000032:analysis; D020346:Aquaporins / Q000032:analysis; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002217:Carbachol / Q000494:pharmacology; D048429:Cell Size; D018679:Cholinergic Agonists / Q000494:pharmacology; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D012463:Saliva / Q000737:chemistry / Q000378:metabolism; D012469:Salivary Glands / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D016037:Single-Blind Method; D012859:Sjogren's Syndrome / Q000473:pathology / Q000503:physiopathology*
C496027:AQP3 protein, human; C496036:AQP5 protein, human; D051402:Aquaporin 5; D020346:Aquaporins; D018679:Cholinergic Agonists; D051398:Aquaporin 1; D051400:Aquaporin 3; D002217:Carbachol
Sjögren's Syndrome; aquaporins; calcium signaling; cell volume regulation; saliva