title: Stretch regulates expression and binding of chymotrypsin-like elastase 1 in the postnatal lung.
abstract: Lung stretch is critical for normal lung development and for compensatory lung growth after pneumonectomy (PNX), but the mechanisms by which strain induces matrix remodeling are unclear. Our prior work demonstrated an association of chymotrypsin-like elastase 1 (Cela1) with lung elastin remodeling, and that strain triggered a near-instantaneous elastin-remodeling response. We sought to determine whether stretch regulates Cela1 expression and Cela1 binding to lung elastin. In C57BL/6J mice, Cela1 protein increased 176-fold during lung morphogenesis. Cela1 was covalently bound to serpin peptidase inhibitor, clade A, member 1, resulting in a higher molecular mass in lung homogenate compared to pancreas homogenate. Post-PNX, Cela1 mRNA increased 6-fold, protein 3-fold, and Cela1-positive cells 2-fold. Cela1 was expressed predominantly in alveolar type II cells in the embryonic lung and predominantly in CD90-positive lung fibroblasts postnatally. During compensatory lung growth, Cela1 expression was induced in nonproliferative mesenchymal cells. In ex vivo mouse lung sections, stretch increased Cela1 binding to lung tissue by 46%. Competitive inhibition with soluble elastin completely abrogated this increase. Areas of stretch-induced elastase activity and Cela1 binding colocalized. The stretch-dependent expression and binding kinetics of Cela1 indicate an important role in stretch-dependent remodeling of the peripheral lung during development and regeneration.
authors.affiliation: *Division of Critical Care Medicine, Division of Developmental Biology, and Division of Pulmonary Biology, Department of Clinical Engineering, and Biomedical Research Internship for Minority Students Program, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA; and Ohio State University College of Veterinary Medicine, Columbus, Ohio, USA.
authors.forename: Rashika
authors.initials: R
authors.lastname: Joshi
authors.affiliation: *Division of Critical Care Medicine, Division of Developmental Biology, and Division of Pulmonary Biology, Department of Clinical Engineering, and Biomedical Research Internship for Minority Students Program, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA; and Ohio State University College of Veterinary Medicine, Columbus, Ohio, USA.
authors.forename: Sheng
authors.initials: S
authors.lastname: Liu
authors.affiliation: *Division of Critical Care Medicine, Division of Developmental Biology, and Division of Pulmonary Biology, Department of Clinical Engineering, and Biomedical Research Internship for Minority Students Program, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA; and Ohio State University College of Veterinary Medicine, Columbus, Ohio, USA.
authors.forename: Montell D
authors.initials: MD
authors.lastname: Brown
authors.affiliation: *Division of Critical Care Medicine, Division of Developmental Biology, and Division of Pulmonary Biology, Department of Clinical Engineering, and Biomedical Research Internship for Minority Students Program, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA; and Ohio State University College of Veterinary Medicine, Columbus, Ohio, USA.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Young
authors.affiliation: *Division of Critical Care Medicine, Division of Developmental Biology, and Division of Pulmonary Biology, Department of Clinical Engineering, and Biomedical Research Internship for Minority Students Program, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA; and Ohio State University College of Veterinary Medicine, Columbus, Ohio, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Batie
authors.affiliation: *Division of Critical Care Medicine, Division of Developmental Biology, and Division of Pulmonary Biology, Department of Clinical Engineering, and Biomedical Research Internship for Minority Students Program, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA; and Ohio State University College of Veterinary Medicine, Columbus, Ohio, USA.
authors.forename: J Matthew
authors.initials: JM
authors.lastname: Kofron
authors.affiliation: *Division of Critical Care Medicine, Division of Developmental Biology, and Division of Pulmonary Biology, Department of Clinical Engineering, and Biomedical Research Internship for Minority Students Program, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA; and Ohio State University College of Veterinary Medicine, Columbus, Ohio, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: *Division of Critical Care Medicine, Division of Developmental Biology, and Division of Pulmonary Biology, Department of Clinical Engineering, and Biomedical Research Internship for Minority Students Program, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA; and Ohio State University College of Veterinary Medicine, Columbus, Ohio, USA.
authors.forename: Timmothy E
authors.initials: TE
authors.lastname: Weaver
authors.affiliation: *Division of Critical Care Medicine, Division of Developmental Biology, and Division of Pulmonary Biology, Department of Clinical Engineering, and Biomedical Research Internship for Minority Students Program, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA; and Ohio State University College of Veterinary Medicine, Columbus, Ohio, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Apsley
authors.affiliation: *Division of Critical Care Medicine, Division of Developmental Biology, and Division of Pulmonary Biology, Department of Clinical Engineering, and Biomedical Research Internship for Minority Students Program, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA; and Ohio State University College of Veterinary Medicine, Columbus, Ohio, USA brian.varisco@cchmc.org.
authors.forename: Brian M
authors.initials: BM
authors.lastname: Varisco
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001696:Biomechanical Phenomena; D002478:Cells, Cultured; D053818:Chymases; D004549:Elastin / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D007668:Kidney / Q000166:cytology / Q000196:embryology; D008168:Lung / Q000166:cytology / Q000502:physiology*; D051379:Mice; D010196:Pancreatic Elastase / Q000235:genetics / Q000378:metabolism*; D018800:Thy-1 Antigens / Q000235:genetics / Q000378:metabolism; D000515:alpha 1-Antitrypsin / Q000235:genetics / Q000378:metabolism
chemical_list: D018800:Thy-1 Antigens; D000515:alpha 1-Antitrypsin; D004549:Elastin; C000608293:CELA1 protein, mouse; D010196:Pancreatic Elastase; D053818:Chymases
keywords: elastin; lung development; lung regeneration; matrix remodeling; mechanical strain