Increased circulating desmosine and age-dependent elastinolysis in idiopathic pulmonary fibrosis
Increased circulating desmosine and age-dependent elastinolysis in idiopathic pulmonary fibrosis
复制标题
特发性肺纤维化患者循环锁链素增加和年龄依赖性弹性蛋白溶解
DOI：
10.1186/s12931-018-0747-6
复制
发表时间：
2018-03-20
影响因子：
5.8
通讯作者：
Janssen, Rob
中科院分区：
文献类型：
--
作者：
de Brouwer, Bart;Drent, Marjolein;Janssen, Rob
虽然慢性阻塞性肺疾病（COPD）和特发性肺纤维化（IPF）从临床角度看似乎是相反的实体，但在这两种肺部疾病中已提出了共同的初始致病步骤。肺气肿是由弹性蛋白酶/抗弹性蛋白酶失衡导致弹性蛋白降解加速引起的。然而，弹性蛋白溶解在IPF患者的肺中也加速。氨基酸锁链素和异锁链素（DES）是弹性蛋白所特有的。在降解过程中，弹性蛋白酶从弹性蛋白纤维释放DES。因此，血液DES水平反映了全身弹性蛋白溶解的速率，并且在COPD中增加。这是第一份描述IPF患者DES水平升高的报告。我们还证明了与年龄相关的DES浓度增加在IPF中增强。我们目前的研究表明，弹性蛋白溶解是COPD和IPF的共同致病步骤。需要进一步研究来确定弹性蛋白加速降解与IPF的相关性，并确定减缓这一过程是否会导致肺纤维化进展减慢并提高IPF患者的生存率。
Although chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) seem to be opposite entities from a clinical perspective, common initial pathogenic steps have been suggested in both lung diseases. Emphysema is caused by an elastase/anti-elastase imbalance leading to accelerated elastin degradation. Elastinolysis is however, also accelerated in the IPF patients' lungs. The amino acids desmosine and isodesmosine (DES) are unique to elastin. During the degradation process, elastases liberate DES from elastin fibers. Blood DES levels consequently reflect the rate of systemic elastinolysis and are increased in COPD. This is the first report describing elevated DES levels in IPF patients. We also demonstrated that the age-related increment of DES concentrations is enhanced in IPF. Our current study suggests that elastinolysis is a shared pathogenic step in both COPD and IPF. Further investigation is required to establish the relevance of accelerated elastin degradation in IPF and to determine whether decelerating this process leads to slower progression of lung fibrosis and better survival for patients with IPF.