title: Gene expression profiling of early-phase Sjögren's syndrome in C57BL/6.NOD-Aec1Aec2 mice identifies focal adhesion maturation associated with infiltrating leukocytes.
abstract: OBJECTIVE
  Despite considerable efforts, the molecular and cellular events in lacrimal gland tissues initiating inflammatory responses leading to keratoconjunctivitis sicca (KCS), autoimmunity, and Sjögren's syndrome (SjS) have yet to be defined. To determine whether altered glandular homeostasis occurs before the onset of autoimmunity, a temporal transcriptome study was carried out in an animal model of primary SjS.
  
  
  METHODS
  Using oligonucleotide microarrays, gene expression profiles were generated for lacrimal glands of C57BL/6.NOD-Aec1Aec2 mice 4 to 20 weeks of age. Pairwise analyses identified genes differentially expressed, relative to their 4-week expression, during the development of SjS-like disease. Statistical analyses defined differentially and coordinately expressed gene sets. The PANTHER (Protein ANalysis THrough Evolutionary Relationships) classification system was used to define annotated biological processes or functions.
  
  
  RESULTS
  Temporal transcript expression profiles of C57BL/6.NOD-Aec1Aec2 lacrimal glands before, or concomitant with, the first appearance of inflammatory cells revealed a highly restricted subset of differentially expressed genes encoding interactive extracellular matrix proteins, fibronectin, integrins, and syndecans. In contrast, genes encoding interepithelial junctional complex proteins defined alterations in tight junctions (TJ), adherens, desmosomes, and gap junctions, suggesting perturbations in the permeability of the paracellular spaces between epithelial barriers. Correlating with this were gene sets defining focal adhesion (FA) maturation and Ras/Raf-Mek/Erk signal transduction. Immunohistochemically, FAs were associated with infiltrating leukocytes and not with lacrimal epithelial cells.
  
  
  CONCLUSIONS
  For the first time, FA maturations are implicated as initial biomarkers of impending autoimmunity in lacrimal glands of SjS-prone mice. Changes in TJ complex genes support an increased movement of cells through paracellular spaces.
authors.affiliation: Department of Oral Biology, College of Dentistry, University of Florida, Gainesville, Florida, USA. peck@pathology.ufl.edu
authors.forename: Ammon B
authors.initials: AB
authors.lastname: Peck
authors.forename: Benjamin T
authors.initials: BT
authors.lastname: Saylor
authors.forename: Linh
authors.initials: L
authors.lastname: Nguyen
authors.forename: Ashok
authors.initials: A
authors.lastname: Sharma
authors.forename: Jin-Xiong
authors.initials: JX
authors.lastname: She
authors.forename: Cuong Q
authors.initials: CQ
authors.lastname: Nguyen
authors.forename: Richard A
authors.initials: RA
authors.lastname: McIndoe
mesh_terms: D000818:Animals; D015551:Autoimmunity / Q000235:genetics; D004846:Epithelial Attachment / Q000276:immunology; D005109:Extracellular Matrix / Q000235:genetics / Q000276:immunology; D005260:Female; D022001:Focal Adhesions / Q000235:genetics* / Q000276:immunology; D020869:Gene Expression Profiling; D007765:Lacrimal Apparatus / Q000276:immunology*; D007962:Leukocytes / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000235:genetics / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D008817:Mice, Mutant Strains; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012859:Sjogren's Syndrome / Q000235:genetics* / Q000276:immunology; D013047:Specific Pathogen-Free Organisms