Severe alterations in expression and localisation of alpha 6 beta 4 integrin in salivary gland acini from patients with Sjogren syndrome
Objectives: 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 a6ß4 integrin. In the present work, mRNA and protein levels of a6ß4 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 a6ß4 were determined by semiquantitative reverse transcriptase (RT)-PCR and western blot analysis, respectively. The subcellular localisation of a6ß4 and laminin were evaluated by confocal microscopy. Results: In patients, no significant differences in a6 and ß4 mRNA levels were detected. However, ß4 integrin protein levels were significantly lower, whereas, changes in a6, were highly variable. In controls, a6ß4 was detected in the basolateral and basal surface of serous and mucous acini, respectively. In patients, alterations in a6ß4 distribution were particularly dramatic for acini with strong basal lamina disorganisation. a6ß4 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 a6ß4 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 a6ß4 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.
|Título según WOS:||Severe alterations in expression and localisation of alpha 6 beta 4 integrin in salivary gland acini from patients with Sjogren syndrome|
|Título según SCOPUS:||Severe alterations in expression and localisation of ?6?4 integrin in salivary gland acini from patients with Sjögren syndrome|
|Título de la Revista:||Annals of the Rheumatic Diseases|
|Editorial:||BMJ Publishing Group|
|Fecha de publicación:||2009|
|Página de inicio:||991|