Karagiannis K, Proklou A, Tsitoura E, Lasithiotaki I, Kalpadaki C, Moraitaki D, Sperelakis I, Kontakis G, Antoniou K M, Tzanakis N
School of Medicine, Laboratory of Molecular and Cellular Pneumonology, University of Crete, Heraklion, Crete, Greece.
Department of Respiratory Medicine, University Hospital of Heraklion, Heraklion, Crete, Greece.
Int J Inflam. 2017;2017:6089425. doi: 10.1155/2017/6089425. Epub 2017 Jul 19.
Defective tissue repair and remodeling are main aspects of Chronic Obstructive Pulmonary Disease (COPD) pathophysiology. Bone marrow mesenchymal stem cells (BM-MSCs) have been implicated in this direction, as their functional impairment and recruitment could possibly contribute to disease development and progression. The present study characterizes for the first time the expression of migration related chemokine receptors and their ligands in BM-MSCs from COPD patients. CXCR4/SDF1a and CCR7/CCL19-CCL21 mRNA levels were evaluated in BM-MSCs obtained from twelve COPD patients and seven healthy donors. SDF1a protein levels in sera and BM-MSCs' conditioned media were also evaluated. CXCR4, SDF1a, CCL19, and CCL21 mRNA levels were significantly reduced in COPD BM-MSCs while CCR7 levels were undetectable. Notably, SDF1a protein levels were marginally elevated in both patient sera and BM-MSCs' conditioned media while the increase in SDF1a serum levels significantly correlated with disease severity in COPD. Our findings show posttranscriptional regulation of SDF1a levels in BM-MSCs of COPD patients and significant downregulation of SDF1a and CXCR4 mRNA indicating an involvement of the SDF1a signaling pathway in the disease pathophysiology.
组织修复和重塑缺陷是慢性阻塞性肺疾病（COPD）病理生理学的主要方面。骨髓间充质干细胞（BM-MSCs）已被认为与这一过程有关，因为它们的功能受损和募集可能会促进疾病的发展和进展。本研究首次对COPD患者骨髓间充质干细胞中与迁移相关的趋化因子受体及其配体的表达进行了表征。对12例COPD患者和7名健康供体的骨髓间充质干细胞中的CXCR4/SDF1a和CCR7/CCL19-CCL21 mRNA水平进行了评估。还评估了血清和骨髓间充质干细胞条件培养基中的SDF1a蛋白水平。COPD患者的骨髓间充质干细胞中CXCR4、SDF1a、CCL19和CCL21 mRNA水平显著降低，而CCR7水平未检测到。值得注意的是，患者血清和骨髓间充质干细胞条件培养基中的SDF1a蛋白水平均略有升高，且SDF1a血清水平的升高与COPD疾病严重程度显著相关。我们的研究结果表明，COPD患者骨髓间充质干细胞中SDF1a水平存在转录后调控，且SDF1a和CXCR4 mRNA显著下调，表明SDF-1α信号通路参与了疾病的病理生理过程。
