Down‐regulation of dysferlin and myoferlin in human airway epithelium: differential effects on cell morphology and adhesion

Abstract

Dysferlin and myoferlin belong to Ferlin protein family known to mediate endomembrane fusion events. Mutations of dysferlin lead to muscular dystrophy. Patients with dysferlinopathy show cardiopulmonary complications, suggesting that dysferlin may have functional roles in the pulmonary system. The high homology of myoferlin to dysferlin proposes that myoferlin may also play a role in lung pathology.ObjectivesTo examine dysferlin and myoferlin expression in human lungs and investigate the effects of silencing these genes in human airway epithelial cells (HAEC).MethodsDysferlin and myoferlin expression was evaluated by immunohistochemistry in human airway sections and by Western blot analysis in HAEC. Localization of dysfelrin and myoferlin in HAEC was studied using immunofluorescent staining. Effects of dysferlin and myoferlin knockdown on the morphology and adhesion of HAEC were also assessed.ResultsBoth dysferlin and myoferlin were present in the epithelium of human airway tissues and cultured HAEC. Dysferlin and myoferlin expression localized at the membrane and cytoplasm of HAEC. Knockdown of myoferlin, but not dysferlin, resulted in cell morphological changes, deficient cell adhesion and decreased the expression of zonular occludens 1 in HAEC.ConclusionPresence of dysferlin and myoferlin suggests they play potential roles in the adhesion of human airway epithelial cells.