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Advances in Mucous Cell Metaplasia

A Plug for Mucus as a Therapeutic Focus in Chronic Airway Disease

¹ Section of Pulmonary and Critical Care, Yale University School of Medicine, New Haven, Connecticut

Correspondence and requests for reprints should be addressed to Lauren Cohn, M.D., Section of Pulmonary and Critical Care, Yale University School of Medicine, New Haven, CT 06520. E-mail: Lauren.cohn{at}yale.edu

Mucous cell metaplasia is induced in response to harmful insults and provides front-line protection to clear the airway of toxic substances and cellular debris. In chronic airway diseases mucous metaplasia persists and results in airway obstruction and contributes significantly to morbidity and mortality. Mucus hypersecretion involves increased expression of mucin genes, and increased mucin production and release. The past decade has seen significant advances in our understanding of the molecular mechanisms by which these events occur. Inflammation stimulates epidermal growth factor receptor activation and IL-13 to induce both Clara and ciliated cells to transition into goblet cells through the coordinated actions of FoxA2, TTF-1, SPDEF, and GABA_AR. Ultimately, these steps lead to up-regulation of MUC5AC expression, and increased mucin in goblet cell granules that fuse to the plasma membrane through actions of MARCKS, SNAREs, and Munc proteins. Blockade of mucus in exacerbations of asthma and chronic obstructive pulmonary disease may affect morbidity. Development of new therapies to target mucus production and secretion are now possible given the advances in our understanding of molecular mechanisms of mucous metaplasia. We now have a greater incentive to focus on inhibition of mucus as a therapy for chronic airway diseases.

Key Words: mucus • goblet cell • airway epithelium • asthma • COPD

CLINICAL RELEVANCE This is a translational review that brings together a decade's worth of studies to enhance our understanding of the processes by which mucous metaplasia occurs in health and chronic airway diseases.

 

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