Role of focal adhesion kinase in lung remodeling of endotoxemic rats
| Autor: | Mariana Cardillo Theobaldo, M. C. Guido, Paolo Cesare Biselli, Ricardo Costa Petroni, Walcy Rosolia Teodoro, Francisco Garcia Soriano, Fatima Abatepaulo, Hermes Vieira Barbeiro |
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| Rok vydání: | 2012 |
| Předmět: |
Lipopolysaccharides
Male Small interfering RNA Pathology medicine.medical_specialty Time Factors Acute Lung Injury Lung injury Biology Pulmonary compliance Critical Care and Intensive Care Medicine Gene Expression Regulation Enzymologic Sepsis Focal adhesion medicine Animals Gene Silencing RNA Small Interfering Rats Wistar Lung Kinase medicine.disease Pulmonary hypertension Endotoxemia Rats medicine.anatomical_structure Focal Adhesion Kinase 1 Emergency Medicine Collagen |
| Zdroj: | Shock (Augusta, Ga.). 37(5) |
| ISSN: | 1540-0514 |
| Popis: | 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)Yinduced 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 target- ing 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. |
| Databáze: | OpenAIRE |
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