BASIC AND TRANSLATIONAL RESEARCH

Severe alterations in expression and localisation of 6β4 integrin in salivary gland acini from patients with Sjögren syndrome

J Velozo¹, S Aguilera², C Alliende¹, P Ewert¹, C Molina³, P Pérez¹, L Leyton^1,4, A Quest^1,4, M Brito¹, S González¹, C Leyton¹, M Hermoso¹, R Romo⁵, M-J González¹

¹ University of Chile, Santiago, Chile
² INDISA Clinic, Santiago, Chile
³ Mayor University, Santiago, Chile
⁴ FONDAP Center for Molecular Studies of the Cell, Faculty of Medicine, University of Chile, Santiago, Chile
⁵ Santa María Clinic, Santiago, Chile

M-J González, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Casilla 70061, Santiago 7, Chile; jgonzale{at}med.uchile.cl

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 6β4 integrin. In the present work, mRNA and protein levels of 6β4 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 6β4 were determined by semiquantitative reverse transcriptase (RT)-PCR and western blot analysis, respectively. The subcellular localisation of 6β4 and laminin were evaluated by confocal microscopy.

Results: In patients, no significant differences in 6 and β4 mRNA levels were detected. However, β4 integrin protein levels were significantly lower, whereas, changes in 6, were highly variable. In controls, 6β4 was detected in the basolateral and basal surface of serous and mucous acini, respectively. In patients, alterations in 6β4 distribution were particularly dramatic for acini with strong basal lamina disorganisation. 6β4 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 6β4 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 6β4 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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