The actin regulator zyxin reinforces airway smooth muscle and accumulates in airways of fatal asthmatics

• Published in: PloS one Vol. 12; no. 3; p. e0171728
• Main Authors: Rosner, Sonia R, Pascoe, Christopher D, Blankman, Elizabeth, Jensen, Christopher C, Krishnan, Ramaswamy, James, Alan L, Elliot, John G, Green, Francis H, Liu, Jeffrey C, Seow, Chun Y, Park, Jin-Ah, Beckerle, Mary C, Paré, Peter D, Fredberg, Jeffrey J, Smith, Mark A
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 09.03.2017; Public Library of Science (PLoS)
• Subjects: Actin; Adolescent; Adult; Animal tissues; Animals; Asthma; Asthma - physiopathology; Biology; Biology and Life Sciences; Bronchial spasm; Bronchospasm; Cancer; Case-Control Studies; Complications and side effects; Critical care; Cytoskeleton; Dietary fiber; Environmental health; Fatalities; Female; Health aspects; Heart; Hospitals; Humans; Lung - physiopathology; Lungs; Male; Medicine; Medicine and Health Sciences; Mice, Inbred C57BL; Mice, Knockout; Molecular modelling; Muscle contraction; Muscle Contraction - physiology; Muscles; Myocytes, Smooth Muscle; Physiological effects; Physiology; Prospective Studies; Proteins; Public health; Respiratory tract; Severity of Illness Index; Sleep disorders; Smooth muscle; Stress Fibers; Young Adult; Zyxin - physiology
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0171728

Bronchospasm induced in non-asthmatic human subjects can be easily reversed by a deep inspiration (DI) whereas bronchospasm that occurs spontaneously in asthmatic subjects cannot. This physiological effect of a DI has been attributed to the manner in which a DI causes airway smooth muscle (ASM) cells to stretch, but underlying molecular mechanisms-and their failure in asthma-remain obscure. Using cells and tissues from wild type and zyxin-/- mice we report responses to a transient stretch of physiologic magnitude and duration. At the level of the cytoskeleton, zyxin facilitated repair at sites of stress fiber fragmentation. At the level of the isolated ASM cell, zyxin facilitated recovery of contractile force. Finally, at the level of the small airway embedded with a precision cut lung slice, zyxin slowed airway dilation. Thus, at each level zyxin stabilized ASM structure and contractile properties at current muscle length. Furthermore, when we examined tissue samples from humans who died as the result of an asthma attack, we found increased accumulation of zyxin compared with non-asthmatics and asthmatics who died of other causes. Together, these data suggest a biophysical role for zyxin in fatal asthma.