Adiponectin attenuates lung fibroblasts activation and pulmonary fibrosis induced by paraquat.
Adiponectin attenuates lung fibroblasts activation and pulmonary fibrosis induced by paraquat.
复制标题
脂联素可减弱百草枯诱发的肺成纤维细胞活化和肺纤维化
DOI：
10.1371/journal.pone.0125169
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Liang ZA
中科院分区：
文献类型：
--
作者：
Yao R;Cao Y;He YR;Lau WB;Zeng Z;Liang ZA
肺纤维化是百草枯中毒最常见的并发症之一，需要更有效的治疗方法。越来越多的证据表明，脂联素(APN)可能是一种很有前途的治疗纤维化疾病的方法。在目前的研究中，我们确定了外源性球形APN亚型是否对PQ处理的小鼠和人肺成纤维细胞的肺纤维化具有保护作用，并剖析了相关的潜在机制。将BALB/C小鼠随机分为对照组、PQ组、PQ+APN低剂量组、PQ+APN高剂量组。分别于PQ处理后3、7、14、21天处死小鼠。通过免疫印迹和实时荧光定量聚合酶链式反应(RT-β)比较不同组间肺组织病理改变。采用双抗体夹心法测定血中基质金属蛋白酶-9和基质金属蛋白酶组织抑制因子-1的水平。人肺成纤维细胞WI-38分为对照组、PQ组、APN组和APN受体(AdipoR)1小干扰RNA(SiRNA)组。在PQ暴露后24、48、72小时收集成纤维细胞进行检测。用Kit-8(CCK-8)和荧光素Annexin V-FITC/PI双标记法检测细胞存活率和凋亡率。用Western印迹和RT-PCR检测III型胶原、AdipoR1和AdipoR2的蛋白和mRNA表达水平。APN治疗可明显降低肺纤维化积分、肺组织转化生长因子-β1、α-SMA的蛋白和基因表达，降低血中MMP9和TIMP-1的含量，并呈剂量依赖关系(p<；0.05)。APN可显著减轻PQ诱导的肺成纤维细胞存活率下降和III型胶原表达上调(p<；0.05)。APN处理可上调WI-38成纤维细胞AdipoR1的表达，但不上调AdipoR2的表达。在PQ暴露的成纤维细胞中，AdipoR1 siRNA取消了APN介导的保护作用。综上所述，我们的数据表明，APN通过抑制肺成纤维细胞的激活，以剂量依赖的方式保护PQ诱导的肺纤维化。人肺成纤维细胞表达功能性AdipoR1，提示APN在未来的临床应用中具有潜在的抗肺纤维化作用。
Pulmonary fibrosis is one of the most common complications of paraquat (PQ) poisoning, which demands for more effective therapies. Accumulating evidence suggests adiponectin (APN) may be a promising therapy against fibrotic diseases. In the current study, we determine whether the exogenous globular APN isoform protects against pulmonary fibrosis in PQ-treated mice and human lung fibroblasts, and dissect the responsible underlying mechanisms. BALB/C mice were divided into control group, PQ group, PQ + low-dose APN group, and PQ + high-dose APN group. Mice were sacrificed 3, 7, 14, and 21 days after PQ treatment. We compared pulmonary histopathological changes among different groups on the basis of fibrosis scores, TGF-β1, CTGF and α-SMA pulmonary content via Western blot and real-time quantitative fluorescence-PCR (RT-PCR). Blood levels of MMP-9 and TIMP-1 were determined by ELISA. Human lung fibroblasts WI-38 were divided into control group, PQ group, APN group, and APN receptor (AdipoR) 1 small-interfering RNA (siRNA) group. Fibroblasts were collected 24, 48, and 72 hours after PQ exposure for assay. Cell viability and apoptosis were determined via Kit-8 (CCK-8) and fluorescein Annexin V-FITC/PI double labeling. The protein and mRNA expression level of collagen type III, AdipoR1, and AdipoR2 were measured by Western blot and RT-PCR. APN treatment significantly decreased the lung fibrosis scores, protein and mRNA expression of pulmonary TGF-β1, CTGF and α-SMA content, and blood MMP-9 and TIMP-1 in a dose-dependent manner (p<0.05). Pretreatment with APN significantly attenuated the reduced cell viability and up-regulated collagen type III expression induced by PQ in lung fibroblasts, (p<0.05). APN pretreatment up-regulated AdipoR1, but not AdipoR2, expression in WI-38 fibroblasts. AdipoR1 siRNA abrogated APN-mediated protective effects in PQ-exposed fibroblasts. Taken together, our data suggests APN protects against PQ-induced pulmonary fibrosis in a dose-dependent manner, via suppression of lung fibroblast activation. Functional AdipoR1 are expressed by human WI-38 lung fibroblasts, suggesting potential future clinical applicability of APN against pulmonary fibrosis.
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DOI：
10.1186/1755-1536-4-2
发表时间：
2011-01-10
期刊：
Fibrogenesis & tissue repair
影响因子：
--
作者：
Keeley EC;Mehrad B;Strieter RM
通讯作者：
Strieter RM
影响因子：
29.4
作者：
Kamada, Y;Tamura, S;Matsuzawa, Y
通讯作者：
Matsuzawa, Y
影响因子：
1.8
作者：
Bronnum, Hasse;Eskildsen, Tilde;Sheikh, Soren Paludan
通讯作者：
Sheikh, Soren Paludan
影响因子：
5.8
作者：
HOET, PHM;LEWIS, CPL;NEMERY, B
通讯作者：
NEMERY, B
DOI：
10.1513/pats.200601-012tk
发表时间：
2006-06-01
期刊：
Proceedings of the American Thoracic Society
影响因子：
--
作者：
Pardo, Annie;Selman, Moises
通讯作者：
Selman, Moises