Atrial natriuretic peptide protects against bleomycin-induced pulmonary fibrosis via vascular endothelial cells in mice : ANP for pulmonary fibrosis.
Atrial natriuretic peptide protects against bleomycin-induced pulmonary fibrosis via vascular endothelial cells in mice : ANP for pulmonary fibrosis.
复制标题
DOI：
10.1186/s12931-016-0492-7
复制
发表时间：
2017-01-03
影响因子：
5.8
通讯作者：
Kangawa K
中科院分区：
文献类型：
--
作者：
Okamoto A;Nojiri T;Konishi K;Tokudome T;Miura K;Hosoda H;Hino J;Miyazato M;Kyomoto Y;Asai K;Hirata K;Kangawa K
肺纤维化是一种以进行性呼吸困难和肺功能恶化为特征的危及生命的疾病。心房利钠肽（ANP）是一种心脏来源的分泌肽，在日本临床上用于治疗急性心力衰竭，对各种器官（包括心脏、血管、肾脏和肺）发挥广泛的保护作用。其治疗特性的特征在于由鸟苷酸环化酶-A（GC-A）受体介导的抗炎和抗纤维化活性。我们假设ANP对博莱霉素（BLM）诱导的小鼠肺纤维化具有抗纤维化和抗炎作用。将小鼠分为三组：正常对照组、BLM+赋形剂组和BLM + ANP组。在BLM给药（1 mg/kg）之前开始给予ANP（0.5 μg/kg/min，通过皮下泵）或溶媒，并持续至处死小鼠。在BLM给药后7或21天，根据组织学结果和支气管肺泡灌洗液分析评估肺中的纤维化变化和炎性细胞浸润。此外，在血管内皮特异性GC-A过表达小鼠中评价了BLM诱导的纤维化和炎症。最后，使用稳定表达GC-A受体的永生化小鼠内皮细胞研究了ANP对转化生长因子-β（TGF-β）信号转导的减弱。BLM治疗后，ANP可明显减少肺纤维化面积和炎性细胞浸润。此外，在血管内皮特异性GC-A过表达小鼠中观察到ANP的类似作用。在培养的小鼠内皮细胞中，ANP减少TGF-β刺激后Smad 2的磷酸化。ANP通过血管内皮细胞对BLM诱导的肺纤维化具有保护作用。
Pulmonary 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. Mice 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. ANP 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. ANP exerts protective effects on BLM-induced pulmonary fibrosis via vascular endothelial cells.
登录
查看更多内容
DOI：
10.1165/rcmb.2013-0152oc
发表时间：
2013-12-01
影响因子：
6.4
作者：
Leach, Heather G.;Chrobak, Izabela;Trojanowska, Maria
通讯作者：
Trojanowska, Maria
影响因子：
5.8
作者：
Kimura T;Nojiri T;Hino J;Hosoda H;Miura K;Shintani Y;Inoue M;Zenitani M;Takabatake H;Miyazato M;Okumura M;Kangawa K
通讯作者：
Kangawa K
影响因子：
3.9
作者：
Piera-Velazquez S;Mendoza FA;Jimenez SA
通讯作者：
Jimenez SA
DOI：
10.3109/08977194.2011.595714
发表时间：
2011-10
期刊：
Growth factors (Chur, Switzerland)
影响因子：
--
作者：
Biernacka A;Dobaczewski M;Frangogiannis NG
通讯作者：
Frangogiannis NG
DOI：
10.1073/pnas.1417273112
发表时间：
2015-03-31
影响因子：
11.1
作者：
Nojiri T;Hosoda H;Tokudome T;Miura K;Ishikane S;Otani K;Kishimoto I;Shintani Y;Inoue M;Kimura T;Sawabata N;Minami M;Nakagiri T;Funaki S;Takeuchi Y;Maeda H;Kidoya H;Kiyonari H;Shioi G;Arai Y;Hasegawa T;Takakura N;Hori M;Ohno Y;Miyazato M;Mochizuki N;Okumura M;Kangawa K
通讯作者：
Kangawa K