Atrial natriuretic peptide protects against bleomycin-induced pulmonary fibrosis via vascular endothelial cells in mice

Abstract

BackgroundPulmonary fibrosis is a life-threatening disease characterized by progressive dyspnea and worsening pulmonary function. Atrial natriuretic peptide (ANP), a heart-derived secretory peptide used clinically in Japan for the treatment of acute heart failure, exerts a wide range of protective effects on various organs, including the heart, blood vessels, kidneys, and lungs. Its therapeutic properties are characterized by anti-inflammatory and anti-fibrotic activities mediated by the guanylyl cyclase-A (GC-A) receptor. We hypothesized that ANP would have anti-fibrotic and anti-inflammatory effects on bleomycin (BLM)-induced pulmonary fibrosis in mice.MethodsMice were divided into three groups: normal control, BLM with vehicle, and BLM with ANP. ANP (0.5 μg/kg/min via osmotic-pump, subcutaneously) or vehicle administration was started before BLM administration (1 mg/kg) and continued until the mice were sacrificed. At 7 or 21 days after BLM administration, fibrotic changes and infiltration of inflammatory cells in the lungs were assessed based on histological findings and analysis of bronchoalveolar lavage fluid. In addition, fibrosis and inflammation induced by BLM were evaluated in vascular endothelium-specific GC-A overexpressed mice. Finally, attenuation of transforming growth factor-β (TGF-β) signaling by ANP was studied using immortalized mouse endothelial cells stably expressing GC-A receptor.ResultsANP significantly decreased lung fibrotic area and infiltration of inflammatory cells in lungs after BLM administration. Furthermore, similar effects of ANP were observed in vascular endothelium–specific GC-A overexpressed mice. In cultured mouse endothelial cells, ANP reduced phosphorylation of Smad2 after TGF-β stimulation.ConclusionsANP exerts protective effects on BLM-induced pulmonary fibrosis via vascular endothelial cells.

Comparative Transcriptome Profiling of Skeletal Muscle from Black Muscovy Duck at Different Growth Stages Using RNA-seq

“…At focal adhesion, the extracellular domain of transmembrane integrin, including α and β subunits, is connected to the extracellular matrix (ECM). The intracellular tail of integrin binds to connexin, and connexin binds to the actin cytoskeleton to perform their related functions [ 82 ]. Therefore, the results of this study will allow us to predict the function of new genes and to explore candidate genes that might play a role in muscle growth and development process in duck.…”

Astaxanthin Suppresses Cigarette Smoke-Induced Emphysema through Nrf2 Activation in Mice

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Neuro-Humoral Disbalance in Chronic Heart Failure: Classic and Modern Perspectives

“…В экспериментальном исследовании японских ученых (2017г) показано, что ANP оказы-вает защитное действие на блеомицин-индуцирован-ный легочный фиброз через сосудистые эндотелиаль-ные клетки, снижая фиброзные изменения и нако-пление воспалительных клеток: отмечено снижение уровней экспрессии IL-6, MCP-1, TIMP1 и IL-1, коллагена 1А. Авторы предполагают, что ANP осла-бляет сигнальный путь TGF-β/Smad2 в эндотелиаль-ных клетках [20].…”