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.

SUBMITTER: Garcia-Posadas L 

PROVIDER: S-EPMC7520664 | biostudies-literature |

REPOSITORIES: biostudies-literature