Cell biology of tight junction structure & function

Despite numerous protein interactions, molecular structure of the tight junction is highly dynamic at steady state. This continual reorganization may explain the selectivity of tight junction permeability and be a critical mechanism of barrier regulation.

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Tight junction physiology and pathophysiology

Molecular characterstics of tight junction composition and structure are altered during disease. Detailed analysis has made it clear that at least two separate aspects of tight junction barrier function are independently modified by pathogenic stimuli.

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Tight junction permeability and disease pathogenesis

Barrier dysfunction is present in patients with Crohn's disease as well as some of their healthy first degree relatives. It has therefore been suggested that increased tight junction permeability (reduced barrier function), which can have profound effects on mucosal homeostasis and immune regulation, contributes to development of inflammatory bowel disease.

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Tight junction dysregulation: Mechanisms and druggability

Myosin light chain kinase-dependent phosphorylation of myosin II regulatory light chain is a critical regulator of tight junction barrier function and is required for tumor necrosis factor-induced barrier loss. Inhibition of this enzyme has potential as a nontoxic therapy to restore the barrier in intestinal disease.

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Jerrold R. Turner, MD, PhD
Departments of Pathology
and Medicine (Gastroenterology)

Brigham and
Women's
Hospital

Harvard
Medical
School

NRB 730
77 Avenue Louis Pasteur
Boston, MA 02115