First Author | García-Posadas L | Year | 2020 |
Journal | Am J Pathol | Volume | 190 |
Issue | 10 | Pages | 2067-2079 |
PubMed ID | 32679229 | Mgi Jnum | J:297480 |
Mgi Id | MGI:6472809 | Doi | 10.1016/j.ajpath.2020.06.013 |
Citation | Garcia-Posadas L, et al. (2020) Lacrimal Gland Myoepithelial Cells Are Altered in a Mouse Model of Dry Eye Disease. Am J Pathol 190(10):2067-2079 |
abstractText | 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 Sjogren 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 alpha-smooth muscle actin-green fluorescent protein that labels MECs. MECs were stimulated with cholinergic and alpha1-adrenergic agonists, vasoactive intestinal peptide (VIP), and the purinergic agonists ATP and UTP. Then intracellular [Ca(2+)] 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 [Ca(2+)]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. |