title: Severe alterations in expression and localisation of {alpha}6{beta}4 integrin in salivary gland acini from patients with Sjogren syndrome.
abstract: OBJECTIVE
  In salivary glands from patients with Sjögren syndrome, overexpression of laminins 1 and 5 and disorganisation of the acinar basal lamina have been reported. Laminin 5 mediates association of the basal lamina with epithelial cells by forming adhesion complexes upon interaction with alpha6beta4 integrin. In the present work, mRNA and protein levels of alpha6beta4 integrin were determined and its localisation in salivary glands evaluated in patients with Sjögren syndrome.
  
  
  METHODS
  Salivary glands of 12 patients with Sjögren syndrome and 8 controls were studied. The mRNA and protein levels of alpha6beta4 were determined by semiquantitative reverse transcriptase (RT)-PCR and western blot analysis, respectively. The subcellular localisation of alpha6beta4 and laminin were evaluated by confocal microscopy.
  
  
  RESULTS
  In patients, no significant differences in alpha6 and beta4 mRNA levels were detected. However, beta4 integrin protein levels were significantly lower, whereas, changes in alpha6, were highly variable. In controls, alpha6beta4 was detected in the basolateral and basal surface of serous and mucous acini, respectively. In patients, alterations in alpha6beta4 distribution were particularly dramatic for acini with strong basal lamina disorganisation. alpha6beta4 was also detected in the cytoplasm and lateral plasma membrane in serous and mucous acini.
  
  
  CONCLUSIONS
  Mild alterations in the basal lamina correlated with lateral redistribution of alpha6beta4 integrin and the formation of new cell-cell adhesions that help maintain acinar organisation and promote cell survival. Conversely, in cases with severe basal lamina alterations, lateral alpha6beta4 redistribution was no longer sufficient to maintain acinar cell survival. Thus, maintenance of equilibrium between cell-cell and cell-basal lamina attachment is required to sustain gland cell survival.
authors.affiliation: University of Chile, Santiago, Chile.
authors.forename: J
authors.initials: J
authors.lastname: Velozo
authors.forename: S
authors.initials: S
authors.lastname: Aguilera
authors.forename: C
authors.initials: C
authors.lastname: Alliende
authors.forename: P
authors.initials: P
authors.lastname: Ewert
authors.forename: C
authors.initials: C
authors.lastname: Molina
authors.forename: P
authors.initials: P
authors.lastname: Pérez
authors.forename: L
authors.initials: L
authors.lastname: Leyton
authors.forename: A
authors.initials: A
authors.lastname: Quest
authors.forename: M
authors.initials: M
authors.lastname: Brito
authors.forename: S
authors.initials: S
authors.lastname: González
authors.forename: C
authors.initials: C
authors.lastname: Leyton
authors.forename: M
authors.initials: M
authors.lastname: Hermoso
authors.forename: R
authors.initials: R
authors.lastname: Romo
authors.forename: M-J
authors.initials: MJ
authors.lastname: González
mesh_terms: D000328:Adult; D000368:Aged; D001485:Basement Membrane / Q000737:chemistry* / Q000378:metabolism; D015153:Blotting, Western; D016022:Case-Control Studies; D002448:Cell Adhesion; D002462:Cell Membrane / Q000737:chemistry / Q000648:ultrastructure; D003593:Cytoplasm / Q000737:chemistry / Q000648:ultrastructure; D015870:Gene Expression; D006801:Humans; D039161:Integrin alpha6beta4 / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D007797:Laminin / Q000032:analysis / Q000235:genetics; D018613:Microscopy, Confocal; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012469:Salivary Glands / Q000737:chemistry* / Q000378:metabolism; D012859:Sjogren's Syndrome / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018709:Statistics, Nonparametric
chemical_list: D039161:Integrin alpha6beta4; D007797:Laminin; D012333:RNA, Messenger