Protective role of cortistatin in pulmonary inflammation and fibrosis
Metadatos
Mostrar el registro completo del ítemAutor
Barriga, Margarita; Benítez, Raquel; Ferraz de Paula, Viviane; García Frutos, Marina; Caro, Marta; Robledo, Gema; O'Valle Ravassa, Francisco Javier; Campos Salinas, Jenny Karina; Delgado, MarioEditorial
John Wiley & Sons
Materia
Acute lung injury Fibroblasts Macrophages Neuropeptide Pulmonary inflammation
Fecha
2021-07-08Referencia bibliográfica
Barriga, M... [et al.] (2021). Protective role of cortistatin in pulmonary inflammation and fibrosis. British Journal of Pharmacology, 1– 21. [https://doi.org/10.1111/bph.15615]
Patrocinador
Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) 12/21767-5; Instituto de Salud Carlos III Spanish Government European Commission SAF2015-67787-RResumen
Background and Purpose: Acute lung injury (ALI), acute respiratory distress syndrome
(ARDS) and pulmonary fibrosis remain major causes of morbidity, mortality
and a healthcare burden in critically ill patient. There is an urgent need to identify
factors causing susceptibility and for the design of new therapeutic agents. Here, we
evaluate the effectiveness 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 exposure 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 identified cortistatin as an endogenous inhibitor of
pulmonary inflammation and fibrosis. Deficiency in cortistatin could be a marker of
poor prognosis in inflammatory/fibrotic pulmonary disorders. Cortistatin-based therapies
could emerge as attractive candidates to treat severe ALI/ARDS, including
SARS-CoV-2-associated ARDS.