Lacrimal Gland Myoepithelial Cells Are Altered in a Mouse Model of Dry Eye Disease.

Abstract

The purpose of this study was to determine the pathogenic changes that occur in myoepithelial cells (MECs) from lacrimal glands of a mouse model of Sjögren syndrome. MECs were cultured from lacrimal glands of C57BL/6J [wild type (WT)] and thrombospondin 1 null (TSP1-/-, alias Thbs1-/-) mice and from mice expressing α-smooth muscle actin-green fluorescent protein that labels MECs. MECs were stimulated with cholinergic and α1-adrenergic agonists, vasoactive intestinal peptide (VIP), and the purinergic agonists ATP and UTP. Then intracellular [Ca2+] was measured using fura-2, and contraction was observed using live cell imaging. Expression of purinergic receptors was determined by Western blot analysis, and mRNA expression was analyzed by microarray. The increase in intracellular [Ca2+]I with VIP and UTP was significantly smaller in MECs from TSP1-/- compared with WT mice. Cholinergic agonists, ATP, and UTP stimulated contraction in MECs, although contraction of MECs from TSP1-/- mice was reduced compared with WT mice. The amount of purinergic receptors P2Y1, P2Y11, and P2Y13 was significantly decreased in MECs from TSP1-/- compared with WT mice, whereas several extracellular matrix and inflammation genes were up-regulated in MECs from TSP1-/- mice. We conclude that lacrimal gland MEC function is altered by inflammation because the functions regulated by cholinergic agonists, VIP, and purinergic receptors are decreased in TSP1-/- compared with WT mice.

• Authors: Laura García-Posadas, Robin R Hodges, Tor P Utheim, Ole Kristoffer Olstad, Vanessa Delcroix, Helen P Makarenkova, Darlene A Dartt
• Journal: The American journal of pathology (Am J Pathol) Vol. 190 Issue 10 Pg. 2067-2079 (10 2020) ISSN: 1525-2191 [Electronic] United States
• PMID: 32679229 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2020 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Chemical References

• Calcium

Topics

• Animals
• Calcium (metabolism)
• Calcium Signaling (physiology)
• Disease Models, Animal
• Dry Eye Syndromes (metabolism, pathology)
• Epithelial Cells (metabolism, pathology)
• Inflammation (metabolism)
• Mice, Inbred C57BL
• Muscle Cells (metabolism, pathology)
• Muscle, Smooth (metabolism)