title: The actin regulator zyxin reinforces airway smooth muscle and accumulates in airways of fatal asthmatics.
abstract: 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.
authors.affiliation: Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: Sonia R
authors.initials: SR
authors.lastname: Rosner
authors.affiliation: University of British Columbia Center for Heart Lung Innovation, St Paul Hospital, Vancouver, British Columbia, Canada.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Pascoe
authors.affiliation: Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah, United States of America.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Blankman
authors.affiliation: Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah, United States of America.
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Jensen
authors.affiliation: Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America.
authors.forename: Ramaswamy
authors.initials: R
authors.lastname: Krishnan
authors.affiliation: Department of Pulmonary Physiology and Sleep Medicine, West Australian Sleep Disorders Research Institute, Sir Charles Gairdner Hospital, Nedlands, West Australia, Australia.|School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia.
authors.forename: Alan L
authors.initials: AL
authors.lastname: James
authors.affiliation: Department of Pulmonary Physiology and Sleep Medicine, West Australian Sleep Disorders Research Institute, Sir Charles Gairdner Hospital, Nedlands, West Australia, Australia.
authors.forename: John G
authors.initials: JG
authors.lastname: Elliot
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Francis H
authors.initials: FH
authors.lastname: Green
authors.affiliation: University of British Columbia Center for Heart Lung Innovation, St Paul Hospital, Vancouver, British Columbia, Canada.
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Liu
authors.affiliation: University of British Columbia Center for Heart Lung Innovation, St Paul Hospital, Vancouver, British Columbia, Canada.
authors.forename: Chun Y
authors.initials: CY
authors.lastname: Seow
authors.affiliation: Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: Jin-Ah
authors.initials: JA
authors.lastname: Park
authors.affiliation: Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah, United States of America.|Department of Biology, University of Utah, Salt Lake City, Utah, United States of America.
authors.forename: Mary C
authors.initials: MC
authors.lastname: Beckerle
authors.affiliation: University of British Columbia Center for Heart Lung Innovation, St Paul Hospital, Vancouver, British Columbia, Canada.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Paré
authors.affiliation: Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Fredberg
authors.affiliation: Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah, United States of America.|Department of Biology, University of Utah, Salt Lake City, Utah, United States of America.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Smith
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D001249:Asthma / Q000503:physiopathology*; D016022:Case-Control Studies; D003599:Cytoskeleton; D005260:Female; D006801:Humans; D008168:Lung / Q000503:physiopathology*; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009119:Muscle Contraction / Q000502:physiology*; D032389:Myocytes, Smooth Muscle; D011446:Prospective Studies; D012720:Severity of Illness Index; D022502:Stress Fibers; D055815:Young Adult; D060589:Zyxin / Q000502:physiology*
chemical_list: D060589:Zyxin