Shinde Arti V, Kelsh Rhiannon, Peters John H, Sekiguchi Kiyotoshi, Van De Water Livingston, McKeown-Longo Paula J
Center for Cell Biology and Cancer Research, Albany Medical College, Albany, NY 12208, United States.
VA Northern California Health Care System and Center for Musculoskeletal Health, Department of Internal Medicine, University of California - Davis School of Medicine, Sacramento, CA, United States.
Matrix Biol. 2015 Jan;41:26-35. doi: 10.1016/j.matbio.2014.11.004. Epub 2014 Nov 26.
Prompt deposition of fibronectin-rich extracellular matrix is a critical feature of normal development and the host-response to injury. Fibronectin isoforms that include the EDA and EDB domains are prominent in these fibronectin matrices. We now report using human dermal fibroblast cultures that the EDA domain of fibronectin or EDA-derived peptides modeled after the C-C' loop promote stress fiber formation and myosin-light chain phosphorylation. These changes are accompanied by an increase in fibronectin synthesis and fibrillogenesis. These effects are blocked by pretreating cells with either siRNA or blocking antibody to the α4 integrin. Our data indicate that the interaction between the α4β1 integrin and the EDA domain of fibronectin helps to drive tissue fibrosis by promoting a contractile phenotype and an increase in fibronectin synthesis and deposition.
富含纤连蛋白的细胞外基质的迅速沉积是正常发育和宿主对损伤反应的关键特征。包含EDA和EDB结构域的纤连蛋白异构体在这些纤连蛋白基质中很突出。我们现在报告，在人真皮成纤维细胞培养中，纤连蛋白的EDA结构域或基于C-C'环模拟的EDA衍生肽可促进应力纤维形成和肌球蛋白轻链磷酸化。这些变化伴随着纤连蛋白合成和纤维形成的增加。用针对α4整合素的siRNA或阻断抗体预处理细胞可阻断这些效应。我们的数据表明，α4β1整合素与纤连蛋白的EDA结构域之间的相互作用通过促进收缩表型以及纤连蛋白合成和沉积的增加来推动组织纤维化。
