title: Role of focal adhesion kinase in lung remodeling of endotoxemic rats.
abstract: Despite significant advances in the care of critically ill patients, acute lung injury continues to be a complex problem with high mortality. The present study was designed to characterize early lipopolysaccharide (LPS)-induced pulmonary injury and small interfering RNA targeting focal adhesion kinase (FAK) as a possible therapeutic tool in the septic lung remodeling process. Male Wistar rats were assigned into endotoxemic group and control group. Total collagen deposition was performed 8, 16, and 24 h after LPS injection. Focal adhesion kinase expression, interstitial and vascular collagen deposition, and pulmonary mechanics were analyzed at 24 h. Intravenous injection of small interfering RNA targeting FAK was used to silence expression of the kinase in pulmonary tissue. Focal adhesion kinase, total collagen deposition, and pulmonary mechanics showed increased in LPS group. Types I, III, and V collagen showed increase in pulmonary parenchyma, but only type V increased in vessels 24 h after LPS injection. Focal adhesion kinase silencing prevented lung remodeling in pulmonary parenchyma at 24 h. In conclusion, LPS induced a precocious and important lung remodeling. There was fibrotic response in the lung characterized by increased amount in total and specific-type collagen. These data may explain the frequent clinical presentation during sepsis of reduced lung compliance, oxygen diffusion, and pulmonary hypertension. The fact that FAK silencing was protective against lung collagen deposition underscores the therapeutic potential of FAK targeting by small interfering RNA.
authors.affiliation: Emergency Medicine Department, Medical School of University of São Paulo, São Paulo, Brazil.
authors.forename: Ricardo Costa
authors.initials: RC
authors.lastname: Petroni
authors.forename: Walcy R
authors.initials: WR
authors.lastname: Teodoro
authors.forename: Maria Carolina
authors.initials: MC
authors.lastname: Guido
authors.forename: Hermes Vieira
authors.initials: HV
authors.lastname: Barbeiro
authors.forename: Fátima
authors.initials: F
authors.lastname: Abatepaulo
authors.forename: Mariana Cardillo
authors.initials: MC
authors.lastname: Theobaldo
authors.forename: Paolo Cesare
authors.initials: PC
authors.lastname: Biselli
authors.forename: Francisco Garcia
authors.initials: FG
authors.lastname: Soriano
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology / Q000628:therapy; D000818:Animals; D003094:Collagen / Q000378:metabolism; D019446:Endotoxemia / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology / Q000628:therapy; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D020868:Gene Silencing; D008070:Lipopolysaccharides / Q000633:toxicity; D008168:Lung / Q000201:enzymology* / Q000473:pathology; D008297:Male; D034741:RNA, Small Interfering; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D008070:Lipopolysaccharides; D034741:RNA, Small Interfering; D003094:Collagen; D051417:Focal Adhesion Kinase 1; C496052:Ptk2 protein, rat