title: Cyclic stretch magnitude and duration affect rat alveolar epithelial gene expression.
abstract: Mechanical ventilation with large tidal volumes can increase lung alveolar permeability and initiate inflammatory responses; but the mechanisms that regulate ventilator-associated lung injury and inflammation remain unclear. Analysis of the genomic response of the lung has been performed in intact lungs ventilated at large tidal volumes. This study is the first to study the genomic response of cultured primary alveolar epithelial cells undergoing large and moderate physiologic cyclic stretch. Responses were dependent on stretch magnitude and duration. Genomic expression was validated for 5 genes of interest: Amphiregulin, Glutamate-Cysteine Ligase Catalytic subunit, Matrix Metalloproteinase 7, Protein Phosphatase 1 regulatory inhibitor subunit 10, and Serpine-1, and protein expression mirrored genomic responses. Differences between results reported from homogenized intact lungs and monolayers of alveolar epithelial cells with type-I like phenotype provide provocative evidence that the whole lung preparation may mask the response of individual cell types.
authors.affiliation: Department of Bioengineering University of Pennsylvania, Philadelphia, USA.
authors.forename: Adi
authors.initials: A
authors.lastname: Yerrapureddy
authors.forename: John
authors.initials: J
authors.lastname: Tobias
authors.forename: Susan S
authors.initials: SS
authors.lastname: Margulies
mesh_terms: D056809:Alveolar Epithelial Cells / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D066258:Amphiregulin; D000818:Animals; D002478:Cells, Cultured; D066255:EGF Family of Proteins; D015870:Gene Expression; D016678:Genome; D005721:Glutamate-Cysteine Ligase / Q000235:genetics / Q000378:metabolism; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000503:physiopathology; D020783:Matrix Metalloproteinase 7 / Q000235:genetics / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism; D054645:Protein Phosphatase 1 / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013314:Stress, Mechanical; D055397:Ventilator-Induced Lung Injury / Q000235:genetics*
chemical_list: C587848:AREG protein, human; D066258:Amphiregulin; C587850:Areg protein, rat; D066255:EGF Family of Proteins; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D017395:Plasminogen Activator Inhibitor 1; C547314:Serpine1 protein, rat; D054645:Protein Phosphatase 1; D020783:Matrix Metalloproteinase 7; D005721:Glutamate-Cysteine Ligase