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• W2169076324 abstract "Rationale: Activin-A is up-regulated in various respiratory disorders. However, its precise role in pulmonary pathophysiology has not been adequately substantiated in vivo.Objectives: To investigate in vivo the consequences of dysregulated Activin-A expression in the lung and identify key Activin-A–induced processes that contribute to respiratory pathology.Methods: Activin-A was ectopically expressed in murine lung, and functional, structural, and molecular alterations were extensively analyzed. The validity of Activin-A as a therapeutic target was demonstrated in animals overexpressing Activin-A or treated with intratracheal instillation of LPS. Relevancy to human pathology was substantiated by demonstrating high Activin-A levels in bronchoalveolar lavage (BAL) samples from patients with acute respiratory distress syndrome (ARDS).Measurements and Main Results: Overexpression of Activin-A in mouse airways caused pulmonary pathology reminiscent of acute lung injury (ALI)/ARDS. Activin-A triggered a lasting inflammatory response characterized by acute alveolar cell death and hyaline membrane formation, sustained up-regulation of high-mobility group box 1, development of systemic hypercoagulant state, reduction of surfactant proteins SpC, SpB, and SpA, decline of lung compliance, transient fibrosis, and eventually emphysema. Therapeutic neutralization of Activin-A attenuated the ALI/ARDS–like pathology induced either by ectopic expression of Activin-A or by intratracheal instillation of LPS. In line with the similarity of the Activin-A–induced phenotype to human ARDS, selective up-regulation of Activin-A was found in BAL of patients with ARDS.Conclusions: Our studies demonstrate for the first time in vivo the pathogenic consequences of deregulated Activin-A expression in the lung, document novel aspects of Activin-A biology that provide mechanistic explanation for the observed phenotype, link Activin-A to ALI/ARDS pathophysiology, and provide the rationale for therapeutic targeting of Activin-A in these disorders." @default.
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• W2169076324 date "2012-02-15" @default.
• W2169076324 modified "2023-10-02" @default.
• W2169076324 title "Activin-A Overexpression in the Murine Lung Causes Pathology That Simulates Acute Respiratory Distress Syndrome" @default.
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• W2169076324 doi "https://doi.org/10.1164/rccm.201105-0784oc" @default.
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