Ceramide mediates lung fibrosis in cystic fibrosis.
Ceramide mediates lung fibrosis in cystic fibrosis.
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DOI：
10.1016/j.bbrc.2013.03.032
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发表时间：
2013-05-17
影响因子：
3.1
通讯作者：
Gulbins, Erich
中科院分区：
文献类型：
--
作者：
Ziobro, Regan;Henry, Brian;Edwards, Michael J.;Lentsch, Alex B.;Gulbins, Erich
肺纤维化是囊性纤维化和慢性阻塞性肺疾病的主要临床问题之一。然而，导致肺纤维化的分子机制的特点不佳，需要定义。在这里，我们证明了神经酰胺在肺中的慢性积累有助于老年囊性纤维化小鼠纤维化的发展。囊性纤维化小鼠神经酰胺的遗传或药理学正常化（通过酸性鞘磷脂酶的杂合性或用酸性鞘磷脂酶的药理学抑制剂长期（6.5个月）治疗小鼠来实现）显著降低肺纤维化的发展。此外，我们的研究表明，长期治疗囊性纤维化小鼠与酸性鞘磷脂酶或酶的遗传杂合性的药理学抑制剂也最大限度地减少囊性纤维化小鼠的肺部炎症细胞因子。该数据确定神经酰胺是囊性纤维化小鼠中与肺纤维化相关的关键分子，并首次证明酸性鞘磷脂酶的长期抑制能够减轻该动物模型中的纤维化和炎症。
Fibrosis of the lung is one of the major clinical problems of cystic fibrosis and chronic obstructive pulmonary disease. However, the molecular mechanisms leading to pulmonary fibrosis are poorly characterized and require definition. Here, we demonstrate that chronic accumulation of ceramide in the lung contributes to the development of fibrosis in aged cystic fibrosis mice. Genetic or pharmacological normalization of ceramide in cystic fibrosis mice, which was achieved by heterozygosity of acid sphingomyelinase or chronic (6.5 month long) treatment of mice with pharmacological inhibitors of acid sphingomyelinase significantly decreased the development of lung fibrosis. Moreover, our studies demonstrate that long-term treatment of cystic fibrosis mice with pharmacological inhibitors of acid sphingomyelinase or genetic heterozygosity of the enzyme also minimizes pulmonary inflammatory cytokines in cystic fibrosis mice. This data identifies ceramide as a key molecule associated with pulmonary fibrosis in cystic fibrosis mice and demonstrate for the first time that prolonged inhibition of acid sphingomyelinase is able to attenuate fibrosis and inflammation in this animal model.
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DOI：
10.1165/ajrcmb.11.6.7946394
发表时间：
1994-12-01
影响因子：
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DOI：
10.1152/ajplung.00408.2010
发表时间：
2011-06-01
影响因子：
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