Matthes Stephanie A, LaRouere Thomas J, Horowitz Jeffrey C, White Eric S
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, 48109-5642, USA.
BMC Pulm Med. 2015 Nov 6;15:140. doi: 10.1186/s12890-015-0137-5.
Idiopathic pulmonary fibrosis (IPF) is an interstitial fibrotic lung disease of unknown origin and without effective therapy characterized by deposition of extracellular matrix by activated fibroblasts in the lung. Fibroblast activation in IPF is associated with Wnt/β-catenin signaling, but little is known about the role of the β-catenin-homologous desmosomal protein, plakoglobin (PG), in IPF. The objective of this study was to assess the functional role of PG in human lung fibroblasts in IPF.
Human lung fibroblasts from normal or IPF patients were transfected with siRNA targeting PG and used to assess cellular adhesion to a fibronectin substrate, apoptosis and proliferation. Statistical analysis was performed using Student's t-test with Mann-Whitney post-hoc analyses and results were considered significant when p < 0.05.
We found that IPF lung fibroblasts expressed less PG protein than control fibroblasts, but that characteristic fibroblast phenotypes (adhesion, proliferation, and apoptosis) were not controlled by PG expression. Consistent with this, normal fibroblasts in which PG was silenced displayed no change in functional phenotype.
We conclude that diminished PG levels in IPF lung fibroblasts do not directly affect certain phenotypic behaviors. Further study is needed to identify the functional consequences of decreased PG in these cells.
特发性肺纤维化（IPF）是一种病因不明且无有效治疗方法的间质性纤维化肺病，其特征是肺内活化的成纤维细胞沉积细胞外基质。IPF中的成纤维细胞活化与Wnt/β-连环蛋白信号传导有关，但关于β-连环蛋白同源桥粒蛋白——桥粒芯蛋白（PG）在IPF中的作用知之甚少。本研究的目的是评估PG在IPF人肺成纤维细胞中的功能作用。
用靶向PG的小干扰RNA（siRNA）转染来自正常或IPF患者的人肺成纤维细胞，并用于评估细胞对纤连蛋白底物的黏附、凋亡和增殖。采用Student's t检验及Mann-Whitney事后分析进行统计学分析，当p < 0.05时，结果被认为具有显著性。
我们发现，IPF肺成纤维细胞表达的PG蛋白比对照成纤维细胞少，但成纤维细胞的特征性表型（黏附、增殖和凋亡）不受PG表达的控制。与此一致的是，PG沉默的正常成纤维细胞功能表型未发生变化。
我们得出结论，IPF肺成纤维细胞中PG水平降低不会直接影响某些表型行为。需要进一步研究来确定这些细胞中PG减少的功能后果。
