title: Lacrimal Gland Inflammation Deregulates Extracellular Matrix Remodeling and Alters Molecular Signature of Epithelial Stem/Progenitor Cells.
abstract: OBJECTIVE
  The adult lacrimal gland (LG) is highly regenerative and is able to repair itself even after substantial damage; however, this ability to regenerate is lost with the development of dry eye conditions in chronically inflamed LGs.This study compares changes in the cell adhesion and cell matrix molecules and stem cell transcription factors in the LGs of healthy mice and of two mouse models of Sjögren's syndrome: nonobese diabetic (NOD) and MRL-lpr/lpr (MRL/lpr) mice during the early stage of inflammation.
  
  
  METHODS
  The LGs from 12- to 13-week-old female MRL/lpr and male NOD mice along with their respective control strains were harvested and divided into three pieces and processed for quantitative (q) RT-PCR and qRT-PCR Arrays, histology, immunohistochemistry, and Western blotting.
  
  
  RESULTS
  The extracellular matrix (ECM) and adhesion molecules RT2-PCR array combined with protein expression data revealed changes in the expression of integrins, matrix metalloproteinases, and other molecules, which are associated largely with invasion, attachment, and expansion of the lymphocytic cells, whereas changes in the stem cell transcription factors revealed substantial decrease in expression of transcription factors associated with epithelial stem/progenitor cell lineage.
  
  
  CONCLUSIONS
  We concluded that the expression of several important ECM components is significantly deregulated in the LG of two murine models of Sjögren's syndrome, suggesting an alteration of the epithelial stem/progenitor cell niche. This may result in profound effects on localization, activation, proliferation, and differentiation of the LG stem/progenitor cells and, therefore, LG regeneration.
authors.affiliation: Department of Cell and Molecular Biology The Scripps Research Institute, La Jolla, California, United States.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Umazume
authors.affiliation: Department of Cell and Molecular Biology The Scripps Research Institute, La Jolla, California, United States.
authors.forename: William M
authors.initials: WM
authors.lastname: Thomas
authors.affiliation: Department of Cell and Molecular Biology The Scripps Research Institute, La Jolla, California, United States.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Campbell
authors.affiliation: Department of Diagnosis and Health Promotion, Tufts University School of Dental Medicine, Boston, Massachusetts, United States.
authors.forename: Hema
authors.initials: H
authors.lastname: Aluri
authors.affiliation: Department of Diagnosis and Health Promotion, Tufts University School of Dental Medicine, Boston, Massachusetts, United States.
authors.forename: Suharika
authors.initials: S
authors.lastname: Thotakura
authors.affiliation: Department of Diagnosis and Health Promotion, Tufts University School of Dental Medicine, Boston, Massachusetts, United States.
authors.forename: Driss
authors.initials: D
authors.lastname: Zoukhri
authors.affiliation: Department of Cell and Molecular Biology The Scripps Research Institute, La Jolla, California, United States.
authors.forename: Helen P
authors.initials: HP
authors.lastname: Makarenkova
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003607:Dacryocystitis / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D007150:Immunohistochemistry; D007765:Lacrimal Apparatus / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D019463:Mice, Inbred MRL lpr; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*