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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

ROLE OF FOCAL ADHESION KINASE IN LUNG REMODELING OF ENDOTOXEMIC RATS

Texto completo
Autor(es):
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]
Número total de Autores: 8
Afiliação do(s) autor(es):
[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
Número total de Afiliações: 2
Tipo de documento: Artigo Científico
Fonte: Shock; v. 37, n. 5, p. 524-530, MAY 2012.
Citações Web of Science: 7
Resumo

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)

Processo FAPESP: 09/03338-7 - Participação da célula B-1 na resposta inflamatória ao lipopolissacarídeo
Beneficiário:Francisco Garcia Soriano
Modalidade de apoio: Auxílio à Pesquisa - Regular
Processo FAPESP: 06/00443-6 - Estudo das alterações gênicas e do remodelamento cardíaco na endotoxemia induzida por lipopolissacarídeo: uso do RNA de interferência como ferrementa terapêutica para as alterações
Beneficiário:Francisco Garcia Soriano
Modalidade de apoio: Auxílio à Pesquisa - Regular