Universities of Giessen and Marburg Lung Center-UGMLC, D-35392 Giessen, Germany.
J Proteomics. 2013 Jun 24;85:109-28. doi: 10.1016/j.jprot.2013.04.033. Epub 2013 May 6.
Among the idiopathic interstitial pneumonias (IIP), the two entities IPF and NSIP seem to be clinically related, but NSIP has a better outcome. The proteomic signatures which distinguish NSIP from IPF remain still elusive. We therefore performed comparative proteomic analysis of peripheral lung tissue from patients with sporadic IPF (n=14) and fibrotic NSIP (fNSIP, n=8) and organ donors (Controls, n=10), by using the 2-dimensional DIGE technique and MALDI-TOF-MS. The study revealed that the proteomic profiles of IPF and fNSIP were quite similar. Among the upregulated proteins in IPF and fNSIP were stress-induced genes involved in the ER stress-pathway, whereas downregulated proteins in IPF and fNSIP included antiapoptotic factors and antifibrotic molecules. The comparison fNSIP versus IPF indicated upregulation of subunits of the proteasome activator complex and antioxidant enzymes of the peroxiredoxin family. We conclude, that only few protein expression changes exist between IPF and fNSIP, and that epithelial ER- and oxidative stress play a major role in the pathogenesis of both diseases. In contrast to IPF, intracellular clearance of ROS and misfolded protein carbonyls seem to be enhanced in fNSIP due to enhanced expression of antioxidant acting proteins, and may explain the better outcome and survival in patients with fNSIP.
IPF and fibrotic NSIP (fNSIP) belong to the idiopathic interstitial pneumonias and are usually fatal, but fNSIP has a better outcome. In order to identify molecular mechanisms and differences between IPF and fNSIP, we herein present results of a comparative proteome analysis of IPF, fNSIP and control lung tissue. Our data including validation experiments suggest that ER stress and a general stress-response as well as the decline of antioxidant capacity in alveolar epithelium is key in the pathogenesis of IPF and fNSIP. In addition, we could observe a signature of an increased alveolar epithelial protection against oxidative and ER-stress in fNSIP as compared to IPF, which could help to explain the better outcome of fNSIP patients.
在特发性间质性肺炎（IIP）中，IPF 和 NSIP 这两种实体似乎在临床上相关，但 NSIP 的预后更好。区分 NSIP 和 IPF 的蛋白质组学特征仍然难以捉摸。因此，我们通过使用 2 维 DIGE 技术和 MALDI-TOF-MS 对来自特发性纤维化性 NSIP（fNSIP，n=8）和散发性特发性肺纤维化（IPF，n=14）患者和器官供体（对照，n=10）的外周肺组织进行了比较蛋白质组学分析。研究表明，IPF 和 fNSIP 的蛋白质组谱非常相似。在 IPF 和 fNSIP 上调的蛋白质中，包括内质网应激途径中的应激诱导基因，而在 IPF 和 fNSIP 下调的蛋白质中，包括抗凋亡因子和抗纤维化分子。fNSIP 与 IPF 的比较表明，蛋白酶体激活复合物的亚基和过氧化物酶家族的抗氧化酶上调。我们得出的结论是，IPF 和 fNSIP 之间仅存在少数蛋白质表达变化，上皮内质网和氧化应激在这两种疾病的发病机制中起主要作用。与 IPF 相反，由于抗氧化作用蛋白表达增强，fNSIP 中 ROS 和错误折叠蛋白羰基的细胞内清除似乎增强，这可能解释了 fNSIP 患者的更好预后和生存率。
IPF 和纤维化性 NSIP（fNSIP）属于特发性间质性肺炎，通常是致命的，但 fNSIP 的预后更好。为了确定 IPF 和 fNSIP 之间的分子机制和差异，我们在此介绍了 IPF、fNSIP 和对照肺组织的比较蛋白质组分析结果。包括验证实验在内的数据表明，内质网应激和一般应激反应以及肺泡上皮抗氧化能力的下降是 IPF 和 fNSIP 发病机制中的关键。此外，我们可以观察到 fNSIP 中肺泡上皮对氧化和 ER 应激的保护作用增加的特征，这可以帮助解释 fNSIP 患者的预后更好。
