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http://purl.uniprot.org/citations/22161160http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/22161160http://www.w3.org/2000/01/rdf-schema#comment"

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."xsd:string
http://purl.uniprot.org/citations/22161160http://purl.org/dc/terms/identifier"doi:10.1164/rccm.201105-0784oc"xsd:string
http://purl.uniprot.org/citations/22161160http://purl.uniprot.org/core/author"Ritvos O."xsd:string
http://purl.uniprot.org/citations/22161160http://purl.uniprot.org/core/author"Foster M."xsd:string
http://purl.uniprot.org/citations/22161160http://purl.uniprot.org/core/author"Pasternack A."xsd:string
http://purl.uniprot.org/citations/22161160http://purl.uniprot.org/core/author"Ritis K."xsd:string
http://purl.uniprot.org/citations/22161160http://purl.uniprot.org/core/author"Sideras P."xsd:string
http://purl.uniprot.org/citations/22161160http://purl.uniprot.org/core/author"Apostolou E."xsd:string
http://purl.uniprot.org/citations/22161160http://purl.uniprot.org/core/author"Protopapadakis E."xsd:string
http://purl.uniprot.org/citations/22161160http://purl.uniprot.org/core/author"Andreakos E."xsd:string
http://purl.uniprot.org/citations/22161160http://purl.uniprot.org/core/author"Giaglis S."xsd:string
http://purl.uniprot.org/citations/22161160http://purl.uniprot.org/core/author"Stavropoulos A."xsd:string
http://purl.uniprot.org/citations/22161160http://purl.uniprot.org/core/author"Xirakia C."xsd:string
http://purl.uniprot.org/citations/22161160http://purl.uniprot.org/core/author"Tzelepis G.E."xsd:string
http://purl.uniprot.org/citations/22161160http://purl.uniprot.org/core/author"Mentzelopoulos S."xsd:string
http://purl.uniprot.org/citations/22161160http://purl.uniprot.org/core/author"Sountoulidis A."xsd:string
http://purl.uniprot.org/citations/22161160http://purl.uniprot.org/core/date"2012"xsd:gYear
http://purl.uniprot.org/citations/22161160http://purl.uniprot.org/core/name"Am J Respir Crit Care Med"xsd:string
http://purl.uniprot.org/citations/22161160http://purl.uniprot.org/core/pages"382-391"xsd:string
http://purl.uniprot.org/citations/22161160http://purl.uniprot.org/core/title"Activin-A overexpression in the murine lung causes pathology that simulates acute respiratory distress syndrome."xsd:string
http://purl.uniprot.org/citations/22161160http://purl.uniprot.org/core/volume"185"xsd:string
http://purl.uniprot.org/citations/22161160http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/22161160
http://purl.uniprot.org/citations/22161160http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/22161160
http://purl.uniprot.org/uniprot/#_A4D1W7-mappedCitation-22161160http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/22161160
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