Inhibition Of Activin Receptor Like Kinase Activation Affects Extracellular Matrix Metabolism After Inflammatory Lung Injury

This study was designed to investigate the extracellular matrix metabolism changes after inflammatory lung injury and to explore the potential roles of Smads signal transduction pathway in pulmonary fibrosis formation with the use of SB431542 as a specific inhibitor for activin receptor-like kinase 5 in an animal model of LPS-induced acute lung injury. The results show that in the acute phase response of LPS-induced inflammatory lung injury, overexpression of proinflammatory cytokines is the major feature and the turnover of extracellular matrix metabolism occurs at a low level. Early inhibition of ALK5 by SB431542 can further increase the expression of proinflammatory cytokines, aggravates LPS-induced inflammatory lung injury. After the acute phase response, proinflammatory cytokine expression is low and extracellular matrix metabolism begins to be brisk. Inhibition of ALK5 has little effect on expression of proinflammatory cytokines, but can raise the transcription levels of MMP-9 mRNA and the content and activity of MMP-9 in lung tissues, which helps to inhibit the interstitial excessive collagen deposition and to reduce pulmonary fibrosis. Our findings indicate that Smads signal transduction pathway is involved in the process of LPS-induced inflammatory lung injury, but only inhibition of the pathway after but not in acute inflammatory response can reduce pulmonary fibrosis.