The copper dependent-lysyl oxidases contribute to the pathogenesis of pulmonary emphysema in chronic obstructive pulmonary disease patients
The copper dependent-lysyl oxidases contribute to the pathogenesis of pulmonary emphysema in chronic obstructive pulmonary disease patients
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DOI：
10.1016/j.jtemb.2017.08.011
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发表时间：
2017-01-01
影响因子：
3.5
通讯作者：
Oztay, Fusun
中科院分区：
文献类型：
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作者：
Besiktepe, Neziha;Kayalar, Ozgecan;Oztay, Fusun
肺气肿 (PE) 中可见弹性纤维生物学异常。铜依赖性赖氨酰氧化酶调节结缔组织中弹性纤维的产生和积累。本研究重点关注赖氨酰氧化酶 (LOX)、LOX 样蛋白 1 (LOXL1) 和 LOXL2 与 PE 发病机制之间的关系。使用来自慢性阻塞性肺病患者 (n = 35) 的有或没有 PE 的肺样本。采用显微镜和生化方法检测弹性蛋白、LOX、LOXL1、LOXL2、缺氧诱导因子 1-α (HIF-1 α)、含铜代谢结构域 1 (COMMD1) 以及磷酸酶和张力蛋白同源物 (PTEN) 的蛋白水平。 HIF-1 α 免疫反应性。此外，肺气肿区域的弹性蛋白、LOX、LOXL1、LOXL2、HIF-1α、COMMD1 和 PTEN 蛋白水平显着低于非肺气肿区域。我们推测 HIF-1 α 水平的降低导致活性 LOX、LOXL1 和 LOXL2 的蛋白质水平降低。这些减少可能会导致弹性纤维生物学异常。 COMMD1 减少诱导的 HIF-1 α 激活和 PTEN 减少诱导的蛋白酶激活可能有助于 PE 的发展。最后，旨在提高 LOX、COMMD1 和 PTEN 蛋白水平的方法可能对治疗 PE 有效。
Abnormalities in the elastic fiber biology are seen in pulmonary emphysema (PE). The copper-dependent lysyl oxidases regulate the production and accumulation of elastic fibers in the connective tissue. This study focused on the relationship between lysyl oxidase (LOX), LOX-like protein 1 (LOXL1), and LOXL2 and PE pathogenesis. Lung samples with or without PE from patients with chronic obstructive lung disease (n = 35) were used. Protein levels of elastin, LOX, LOXL1, LOXL2, hypoxia inducible factor 1-alpha (HIF-1 alpha), copper metabolism domain containing-1 (COMMD1), and phosphatase and tensin homolog (PTEN) were assayed using microscopic and biochemical methods The emphysematous areas were characterized by enlargement of the alveoli, destruction of the alveolar structure, accumulation of macrophages in the alveolar lumens, and showed increased HIF-1 alpha immunoreactivity. Additionally, the emphysematous areas had significantly lower elastin, LOX, LOXL1, LOXL2, HIF-1 alpha, COMMD1, and PTEN protein levels than the non-emphysematous areas. We suppose that the reductions in the HIF-1 alpha levels led to decreases in the protein levels of active LOX, LOXL1, and LOXL2. These decreases might cause abnormalities in the elastic fiber biology. HIF-1 alpha activation induced by decreased COMMD1 and protease activation induced by decreased PTEN might contribute to the development of PE. Finally, methods aimed at increasing the protein levels of LOXs, COMMD1 and PTEN might be effective for treating PE.