Ge Qi, Chen Ling, Jaffar Jade, Argraves William Scott, Twal Waleed O, Hansbro Phil, Black Judith L, Burgess Janette K, Oliver Brian
1] Respiratory Cellular and Molecular Biology Group, Woolcock Institute of Medical Research, Sydney, NSW 2037, Australia [2] Discipline of Pharmacology, Sydney Medical School, The University of Sydney, NSW 2006, Australia.
Respiratory Cellular and Molecular Biology Group, Woolcock Institute of Medical Research, Sydney, NSW 2037, Australia.
Sci Rep. 2015 Apr 2;5:9496. doi: 10.1038/srep09496.
Fibulin-1 is an extracellular matrix (ECM) protein, levels of which are elevated in serum and lung tissue from patients with idiopathic pulmonary fibrosis compared to healthy volunteers. Inhibition of fibulin-1C, one of four fibulin-1 isoforms, reduced proliferation and wound healing in human airway smooth muscle (ASM) cells. This study identified the bioactive region/s of fibulin-1C which promotes fibrosis. Seven fibulin-1C peptides were synthesized and used to pre-coat tissue culture plates before lung derived ASM cells and fibroblasts from patients with pulmonary fibrosis (PF), chronic obstructive pulmonary disease (COPD) or neither disease (Control) were plated. Peptide effects on in vitro measures of fibrosis: cell attachment, proliferation and viability, and ECM deposition, were examined. Among these peptides, peptide 1C1 (FBLN1C1) enhanced ASM cell and fibroblast attachment. FBLN1C1 increased mitochondrial activity and proliferation in fibroblasts. In addition, FBLN1C1 stimulated fibulin1 deposition in PF and COPD fibroblasts, and augmented fibronectin and perlecan deposition in all three groups. Peptides FBLN1C2 to FBLN1C7 had no activity. The active fibulin-1C peptide identified in this study describes a useful tool for future studies. Ongoing investigation of the role of fibulin-1 may reveal the mechanisms underlying the pathphysiology of chronic lung diseases.
纤连蛋白-1是一种细胞外基质（ECM）蛋白，与健康志愿者相比，特发性肺纤维化患者血清和肺组织中该蛋白水平升高。纤连蛋白-1有四种亚型，其中纤连蛋白-1C的抑制可降低人气道平滑肌（ASM）细胞的增殖和伤口愈合能力。本研究确定了纤连蛋白-1C促进纤维化的生物活性区域。合成了七种纤连蛋白-1C肽，并在接种来自肺纤维化（PF）、慢性阻塞性肺疾病（COPD）患者或无疾病患者（对照）的肺源性ASM细胞和成纤维细胞之前，用这些肽预包被组织培养板。研究了这些肽对纤维化体外指标的影响：细胞黏附、增殖和活力以及ECM沉积。在这些肽中，肽1C1（FBLN1C1）增强了ASM细胞和成纤维细胞的黏附。FBLN1C1增加了成纤维细胞的线粒体活性和增殖。此外，FBLN1C1刺激了PF和COPD成纤维细胞中纤连蛋白1的沉积，并增加了所有三组中纤连蛋白和基底膜聚糖的沉积。肽FBLN1C2至FBLN1C7无活性。本研究中鉴定出的具有活性的纤连蛋白-1C肽为未来的研究提供了一个有用的工具。对纤连蛋白-1作用的持续研究可能会揭示慢性肺病病理生理学背后的机制。
