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Reduced sulfation of MUC5B is linked to xerostomia in Sjögren's Syndrome patients
  1. Cecilia Alliende (ceciliaalliende{at}yahoo.com)
  1. University of Chile, Faculty of Medicine, Chile
    1. Yoon-Jeoung Kwon (yoonjeoung.kwon{at}gmail.com)
    1. University of Chile, Faculty of Medicine, Chile
      1. Mónica Brito (mibritow{at}gmail.com)
      1. University of Chile, Faculty of Medicine, Chile
        1. Claudio Molina (clmolina{at}gmail.com)
        1. Mayor University, Faculty of Dentistry, Chile
          1. Sergio Aguilera (carolinaaguilerap{at}hotmail.com)
          1. INDISA Clinic, Chile
            1. Paola Pérez (pperezriv{at}gmail.com)
            1. University of Chile, Faculty of Medicine, Chile
              1. Lisette Leyton (lleyton{at}med.uchile.cl)
              1. University of Chile, Faculty of Medicine, Chile
                1. Andrew FG Quest (aquest{at}med.uchile.cl)
                1. University of Chile, Faculty of Medicine, Chile
                  1. Ulla Mandel (um{at}odont.ku.dk)
                  1. Faculty of Health Sciences, University of Copenhagen, Denmark
                    1. Enno Veerman (eci.veerman{at}vumc.nl)
                    1. Academic Centre for Dentistry Amsterdam (ACTA), Vrije Universiteit and Universiteit van Amsterdam, Netherlands
                      1. Marisol Espinosa (espinosamar{at}hotmail.com)
                      1. University of Chile, Faculty of Medicine, Chile
                        1. Henrik Clausen (hc{at}imbg.ku.dk)
                        1. Faculty of Health Sciences, University of Copenhagen, Denmark
                          1. Cecilia Leyton (cleyton{at}med.uchile.cl)
                          1. University of Chile, Faculty of Medicine, Chile
                            1. Rafael Romo (el_molix{at}yahoo.com)
                            1. Santa María Clinic, Chile
                              1. María-Julieta Gonzalez (jgonzale{at}med.uchile.cl)
                              1. University of Chile, Faculty of Medicine, Chile

                                Abstract

                                Objectives: MUC5B contains sulfated and sialylated oligosaccharides that sequester water required for moisturizing the oral mucosa. Xerostomia, in Sjögren's syndrome patients, is generally associated with reduced quantities rather than altered properties of saliva. Here, we determined the amount of MUC5B (mRNA and protein) as well as sulfation levels in salivary glands of patients with normal or altered unstimulated salivary flow. Localization of MUC5B and sulfated MUC5B, as well as total levels sulfated groups were determined and compared with acini basal lamina disorganization.

                                Patients and Methods: Eighteen patients with normal or altered unstimulated salivary flow and 16 controls were studied. MUC5B mRNA and protein were evaluated in salivary glands by semiquantitative-RT-PCR and Western blot analysis. MUC5B sulfation was determined by Western blotting. MUC5B and sulfo-Lewisa antigen localization were assessed by immunohistochemistry. The total amount of sulfated oligosaccharides was determined microdensitometrically.

                                Results: No significant differences were detected in MUC5B mRNA and protein levels between controls and patients, while sulfo-Lewisa antigen levels were lower in patients. The number of sulfo-Lewisa positive mucous acini was reduced in patients but no correlation was observed between lower levels of sulfation and unstimulated salivary flow. Microdensitometric data confirmed the presence of reduced sulfated oligosaccharides levels in mucous acini from patients with highly disorganized basal-lamina.

                                Conclusion: Disorganization of the basal-lamina observed in Sjögren's syndrome patients may lead to dedifferentiation of acinar mucous cells and, as a consequence, alter sulfation of MUC5B. These changes are suggested to represent a novel mechanism that may explain xerostomia in these patients.

                                • MUC5B desulfation
                                • Sjögren's syndrome
                                • basal lamina
                                • salivary glands
                                • xerostomia

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