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Severe alterations in expression and localization of α6β4 integrin in salivary gland acini from Sjögren’s syndrome patients
  1. José Velozo (josevelozo{at}terra.cl)
  1. Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Chile
    1. Sergio Aguilera (carolinaaguilerap{at}hotmail.com)
    1. INDISA Clinic, Chile
      1. Cecilia Alliende (ceciliaalliende{at}yahoo.com)
      1. Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Chile
        1. Patricia Ewert (patricia.ewert{at}gmail.com)
        1. Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Chile
          1. Claudio Molina (clmolina{at}gmail.com)
          1. Mayor University, Chile
            1. Paola Pérez (pperezriv{at}gmail.com)
            1. Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Chile
              1. Lisette Leyton (lleyton{at}med.uchile.cl)
              1. Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Chile
                1. Andrew Quest (aquest{at}med.uchile.cl)
                1. Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Chile
                  1. Mónica Brito (mbrito{at}med.uchile.cl)
                  1. Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Chile
                    1. Sergio González (sergiogprovidell{at}yahoo.com)
                    1. Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Chile
                      1. Cecilia Leyton (cleyton{at}med.uchile.cl)
                      1. Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Chile
                        1. Marcela Hermoso (mhermoso{at}med.uchile.cl)
                        1. Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Chile
                          1. Rafael Romo (el_molix{at}yahoo.com)
                          1. Santa María Clinic, Chile
                            1. María-Julieta González (jgonzale{at}med.uchile.cl)
                            1. Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Chile

                              Abstract

                              Objectives: In salivary glands from Sjögren’s syndrome patients, overexpression of laminin-1 and -5 and disorganization 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 α6&beta]4 integrin. Here, we determine mRNA and protein levels of α6β4 integrin and evaluate its localization in salivary glands from Sjögren’s syndrome patients.

                              Methods: Salivary glands of 12 Sjögren’s syndrome patients and 8 controls were studied. The mRNA and protein levels of α6β4 were determined by semiquantitative RT-PCR and Western blot analysis, respectively. The subcellular localization of α6β4 and laminin were evaluated by confocal microscopy.

                              Results: In patients, no significant differences in α6 and β4 mRNA levels were detected. However, β4 integrin protein levels were significantly lower, whereas, changes in α6, were highly variable. In controls, α6β4 was detected in the basolateral and basal surface of serous and mucous acini, respectively. In patients, alterations in α6β4 distribution were particularly dramatic for acini with strong basal lamina disorganization. α6β4 was also detected in the cytoplasm and lateral plasma membrane in serous and mucous acini.

                              Conclusion: Mild alterations in the basal lamina correlated with lateral redistribution of α6β4 integrin, and the formation of new cell-cell adhesions that help maintain acinar organization and promote cell survival. Conversely, in cases with severe basal lamina alterations, lateral α6β4 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.

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