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.