title: Localization and stretch-dependence of lung elastase activity in development and compensatory growth.
abstract: Synthesis and remodeling of the lung matrix is necessary for primary and compensatory lung growth. Because cyclic negative force is applied to developing lung tissue during the respiratory cycle, we hypothesized that stretch is a critical regulator of lung matrix remodeling. By using quantitative image analysis of whole-lung and whole-lobe elastin in situ zymography images, we demonstrated that elastase activity increased twofold during the alveolar stage of postnatal lung morphogenesis in the mouse. Remodeling was restricted to alveolar walls and ducts and was nearly absent in dense elastin band structures. In the mouse pneumonectomy model of compensatory lung growth, elastase activity increased threefold, peaking at 14 days postpneumonectomy and was higher in the accessory lobe compared with other lobes. Remodeling during normal development and during compensatory lung growth was different with increased major airway and pulmonary arterial remodeling during development but not regeneration, and with homogenous remodeling throughout the parenchyma during development, but increased remodeling only in subpleural regions during compensatory lung growth. Left lung wax plombage prevented increased lung elastin during compensatory lung growth. To test whether the adult lung retains an innate capacity to remodel elastin, we developed a confocal microscope-compatible stretching device. In ex vivo adult mouse lung sections, lung elastase activity increased exponentially with strain and in peripheral regions of lung more than in central regions. Our study demonstrates that lung elastase activity is stretch-dependent and supports a model in which externally applied forces influence the composition, structure, and function of the matrix during periods of alveolar septation.
authors.affiliation: College of Veterinary Medicine, The Ohio State University, Columbus, Ohio;
authors.forename: Sarah Marie
authors.initials: SM
authors.lastname: Young
authors.affiliation: Division of Critical Care Medicine, Cincinnati Children's Hospital, Cincinnati, Ohio; Department of Pediatrics, Cincinnati Children's Hospital, Cincinnati, Ohio.
authors.forename: Sheng
authors.initials: S
authors.lastname: Liu
authors.affiliation: Division of Critical Care Medicine, Cincinnati Children's Hospital, Cincinnati, Ohio; Department of Pediatrics, Cincinnati Children's Hospital, Cincinnati, Ohio.
authors.forename: Rashika
authors.initials: R
authors.lastname: Joshi
authors.affiliation: Clinical Engineering, Cincinnati Children's Hospital, Cincinnati, Ohio;
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Batie
authors.affiliation: Department of Developmental Biology, Cincinnati Children's Hospital, Cincinnati, Ohio;
authors.forename: Matthew
authors.initials: M
authors.lastname: Kofron
authors.affiliation: Center for Pulmonary Imaging Research, Cincinnati Children's Hospital, Cincinnati, Ohio;
authors.forename: Jinbang
authors.initials: J
authors.lastname: Guo
authors.affiliation: Center for Pulmonary Imaging Research, Cincinnati Children's Hospital, Cincinnati, Ohio; Department of Radiology, Cincinnati Children's Hospital, Cincinnati, Ohio; and Department of Pediatrics, Cincinnati Children's Hospital, Cincinnati, Ohio.
authors.forename: Jason C
authors.initials: JC
authors.lastname: Woods
authors.affiliation: Division of Critical Care Medicine, Cincinnati Children's Hospital, Cincinnati, Ohio; Department of Pediatrics, Cincinnati Children's Hospital, Cincinnati, Ohio brian.varisco@cchmc.org.
authors.forename: Brian Michael
authors.initials: BM
authors.lastname: Varisco
mesh_terms: D000818:Animals; D055119:Elastic Modulus / Q000502:physiology; D004789:Enzyme Activation; D066298:In Vitro Techniques; D008168:Lung / Q000201:enzymology* / Q000254:growth & development*; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009024:Morphogenesis / Q000502:physiology*; D010196:Pancreatic Elastase / Q000502:physiology*; D013314:Stress, Mechanical; D013718:Tensile Strength / Q000502:physiology; D014018:Tissue Distribution
chemical_list: D010196:Pancreatic Elastase
keywords: elastin; lung development; lung regeneration; protease; stretch