Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/246958
Share/Export:
logo share SHARE logo core CORE BASE
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE
Title

Protective Role of Cortistatin in Pulmonary Inflammation and Fibrosis

Other TitlesCortistatin protects from experimental ALI/ARDS
AuthorsBarriga, Margarita; Benitez, Raquel; Ferraz-de-Paula, Viviane; Garcia-Frutos, Marina; Caro, Marta; Robledo, Gema; O’Valle, Francisco4; Campos-Salinas, Jenny; Delgado, Mario
KeywordsAcute lung injury
Pulmonary inflammation
Fibroblasts
Macrophages
Neuropeptide
Issue Date8-Jul-2021
PublisherJohn Wiley & Sons
CitationBritish Journal of Pharmacology (2021)
AbstractBackground and Purpose Acute lung injury (ALI), acute respiratory distress syndrome (ARDS) and pulmonary fibrosis remain major causes of morbidity, mortality and healthcare burden in the critically ill patient. There is an urgent medical need for identifying factors of susceptibility and prognosis and for designing new therapeutic tools for treating these disorders. Here, we evaluate the capacity of the immunomodulatory neuropeptide cortistatin to regulate pulmonary inflammation and fibrosis in vivo. Experimental Approach ALI/ARDS and pulmonary fibrosis were induced experimentally in wild-type and cortistatin-deficient mice by pulmonary infusion of the bacterial endotoxin LPS or the chemotherapeutic drug bleomycin, and the histopathological signs, pulmonary leukocyte infiltration and cytokines and fibrotic markers were evaluated. Key Results Partially-deficient mice in cortistatin showed exacerbated pulmonary damage, pulmonary inflammation, alveolar oedema and fibrosis, and subsequent increased respiratory failure and mortality when challenged to LPS or bleomycin, even at low doses. Treatment with cortistatin reversed these aggravated phenotypes and protected from progression to severe ARDS and fibrosis after high-exposition to both injury agents. Moreover, cortistatin-deficient pulmonary macrophages and fibroblasts showed exaggerated ex vivo inflammatory and fibrotic responses, and treatment with cortistatin impaired their activation. Finally, the protective effects of cortistatin in ALI and pulmonary fibrosis were partially inhibited by specific antagonists for somatostatin- and ghrelin-receptors. Conclusion and Implications We identify to cortistatin as an endogenous break of pulmonary inflammation and fibrosis. Deficiency in cortistatin could be a marker of poor-prognosis in inflammatory/fibrotic pulmonary disorders. Cortistatin-based therapies emerge as attractive candidates to treat severe ALI/ARDS, including SARS-Cov-2-associated ARDS.
Publisher version (URL)https://doi.org/10.1111/bph.15615
URIhttp://hdl.handle.net/10261/246958
DOI10.1111/bph.15615
ISSN0007-1188
E-ISSN1476-5381
Appears in Collections:(VICYT) Colección Especial COVID-19
(IPBLN) Artículos

Files in This Item:
File Description SizeFormat
accesoRestringido.pdf15,38 kBAdobe PDFThumbnail
View/Open
Show full item record
Review this work

SCOPUSTM   
Citations

2
checked on Jan 11, 2022

WEB OF SCIENCETM
Citations

1
checked on Jan 16, 2022

Page view(s)

63
checked on Jan 19, 2022

Download(s)

12
checked on Jan 19, 2022

Google ScholarTM

Check

Altmetric

Dimensions


WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.