Hohensinner P J, Kaun C, Rychli K, Niessner A, Pfaffenberger S, Rega G, Furnkranz A, Uhrin P, Zaujec J, Afonyushkin T, Bochkov V N, Maurer G, Huber K, Wojta J
Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria.
FASEB J. 2009 Mar;23(3):774-82. doi: 10.1096/fj.08-108035. Epub 2008 Nov 19.
Stromal derived factor 1 (SDF-1) is a CXC chemokine important in the homing process of stem cells to injured tissue. It has been implicated in healing and tissue repair. Growing evidence suggests that the glycoprotein-130 (gp130) ligand family is involved in repair processes in the heart. The aim of our study was to determine whether gp130 ligands could affect SDF-1 expression in cardiac cells. Human adult cardiac myocytes (HACMs) and fibroblasts (HACFs) were treated with gp130 ligands. Protein and mRNA levels of SDF-1 were determined using ELISA and RT-PCR, respectively. mRNA levels of SDF-1 were determined in human and mouse heart samples by RT-PCR. HACMs and HACFs constitutively express SDF-1, which was significantly up-regulated by the gp130 ligand oncostatin M (OSM). This effect was counteracted by a p38 inhibitor and to a lesser extent by a PI3K inhibitor. mRNA expression of SDF-1 in hearts of mice injected with OSM increased significantly. Levels of OSM and SDF-1 mRNA correlated significantly in human failing hearts. Our data, showing that OSM induces SDF-1 protein secretion in human cardiac cells in vitro and murine hearts in vivo, suggest that OSM via the induction of SDF-1 might play a key role in repair and tissue regeneration.
基质衍生因子1（SDF-1）是一种CXC趋化因子，在干细胞归巢至损伤组织的过程中起重要作用。它与愈合和组织修复有关。越来越多的证据表明，糖蛋白130（gp130）配体家族参与心脏的修复过程。我们研究的目的是确定gp130配体是否会影响心脏细胞中SDF-1的表达。用gp130配体处理成人心脏心肌细胞（HACM）和成纤维细胞（HACF）。分别使用酶联免疫吸附测定（ELISA）和逆转录聚合酶链反应（RT-PCR）测定SDF-1的蛋白质和mRNA水平。通过RT-PCR测定人和小鼠心脏样本中SDF-1的mRNA水平。HACM和HACF组成性表达SDF-1，其被gp130配体制瘤素M（OSM）显著上调。这种作用被p38抑制剂抵消，在较小程度上被磷脂酰肌醇-3-激酶（PI3K）抑制剂抵消。注射OSM的小鼠心脏中SDF-1的mRNA表达显著增加。在人类衰竭心脏中，OSM和SDF-1 mRNA水平显著相关。我们的数据表明，OSM在体外可诱导人心脏细胞和体内小鼠心脏中SDF-1蛋白分泌，提示OSM通过诱导SDF-1可能在修复和组织再生中起关键作用。
