title: Cyclic mechanical stretch inhibits cell proliferation and induces apoptosis in fetal rat lung fibroblasts.
abstract: Development of the pulmonary air sacs is crucial for extrauterine survival. Late fetal lung development is characterized by a thinning of the mesenchyme, which brings pneumocytes and endothelial cells into apposition. We hypothesized that mechanical stretch, simulating fetal breathing movements, plays an important role in this remodeling process. Using a Flexercell Strain Unit, we analyzed the effects of intermittent stretch on cell proliferation and apoptosis activation in fibroblasts isolated from fetal rat lungs during late development. On day 19, intermittent stretch increased cells in G(0)/G(1) by 22% (P = 0.001) and decreased in S phase by 50% (P = 0.003) compared with unstretched controls. Cell proliferation analyzed by 5-bromo-2'-deoxyuridine incorporation showed a similar magnitude of cell cycle arrest (P = 0.04). At this same gestational age, stretch induced apoptosis by two- to threefold over controls, assayed by DNA flow cytometry, terminal deoxynucleotidyl transferase-mediated dUTP-FITC nick-end labeling, and caspase-3 activation. These results indicate that mechanical stretch of fibroblasts isolated during the canalicular stage inhibits cell cycle progression and activates apoptosis. These findings are cotemporal with the mesenchymal thinning that normally occurs in situ.
authors.affiliation: Department of Pediatrics, Women & Infants' Hospital of Rhode Island and Brown Medical School, Providence, Rhode Island 02905, USA. jsesteba@wihri.org
authors.forename: Juan
authors.initials: J
authors.lastname: Sanchez-Esteban
authors.forename: Yulian
authors.initials: Y
authors.lastname: Wang
authors.forename: Lawrence A
authors.initials: LA
authors.lastname: Cicchiello
authors.forename: Lewis P
authors.initials: LP
authors.lastname: Rubin
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D005314:Embryonic and Fetal Development; D004789:Enzyme Activation / Q000502:physiology; D053222:Fas Ligand Protein; D005333:Fetus / Q000166:cytology / Q000502:physiology; D005347:Fibroblasts / Q000502:physiology*; D008168:Lung / Q000196:embryology*; D008562:Membrane Glycoproteins / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013314:Stress, Mechanical; D013997:Time Factors; D019014:fas Receptor / Q000235:genetics
chemical_list: D053222:Fas Ligand Protein; C505662:Faslg protein, rat; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D019014:fas Receptor; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases