ROLE OF FOCAL ADHESION KINASE IN LUNG REMODELING OF ENDOTOXEMIC RATS

Author(s)

Petroni, Ricardo Costa ^[1] ; Teodoro, Walcy R. ^[2] ; Guido, Maria Carolina ^[1] ; Barbeiro, Hermes Vieira ^[1] ; Abatepaulo, Fatima ^[1] ; Theobaldo, Mariana Cardillo ^[1] ; Biselli, Paolo Cesare ^[1] ; Soriano, Francisco Garcia ^[1]

Affiliation

^[1] Univ Sao Paulo, Sch Med, Dept Emergency Med, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Sch Med, Div Rheumatol, Dept Internal Med, Sao Paulo - Brazil

• Document type: Journal article
• Source: Shock; v. 37, n. 5, p. 524-530, MAY 2012.
• Web of Science Citations: 7

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. (AU)

• FAPESP's process: 09/03338-7 - Role of B-1 cell in the inflammatory response deflagrated by lipopolysacharide
• Grantee: Francisco Garcia Soriano
• Support Opportunities: Regular Research Grants
• FAPESP's process: 06/00443-6 - Cardiac remodeling and genic changes induced by LPS: RNAi for terapeuctic use in heart dysfunction
• Grantee: Francisco Garcia Soriano
• Support Opportunities: Regular Research Grants