Zervolea Irene, Pratsinis Harris, Tsagarakis Stylianos, Karavitaki Niki, Stathakos Dimitri, Thalassinos Nikos, Kletsas Dimitris
Laboratory of Cell Proliferation and Ageing, Institute of Biology, National Centre for Scientific Research 'Demokritos', 15310 Athens, Greece.
Eur J Endocrinol. 2005 Jun;152(6):895-902. doi: 10.1530/eje.1.01913.
Chronic exposure to elevated glucocorticoid (GC) concentrations induces detrimental effects in several tissues. In the skin, GCs provoke intense alterations on various parameters of the physiology of fibroblasts, cumulatively leading to skin atrophy and impaired wound healing. As there are concerns that GCs may generate permanent adverse functional changes, we have investigated whether chronic in vivo exposure to GC excess results in persisting defects in skin fibroblasts.
We have studied in vitro primary skin fibroblast cultures obtained from patients suffering from endogenous Cushing's syndrome (CF), as well as from sex- and age-matched normal donors (NF). The following functional parameters were investigated: cell proliferation, secretion of collagen, matrix metalloproteinases (MMPs) and their inhibitors (tissue inhibitors of metalloproteinases; TIMPs) and contractile capacity.
CFs, grown under standard culture conditions in the absence of a hypercortisolemic milieu, exhibited an increased proliferative capacity and a higher final cell culture density compared with NFs. Collagen synthesis, in the absence or presence of transforming growth factor-beta, was equal to that of NFs. However, CFs secreted comparatively lower levels of MMP-1, MMP-2 and TIMP-1, and nearly equal levels of TIMP-2. CFs also exhibited an increased ability to contract gels of polymerized collagen.
Collectively, these functional characteristics of CFs are in contrast to the known catabolic effects of GCs, and suggest that prior exposure to GC excess is not associated with a persisting adverse outcome in the functional phenotype of the fibroblasts.
长期暴露于升高的糖皮质激素(GC)浓度会在多个组织中产生有害影响。在皮肤中,GC会对成纤维细胞生理学的各种参数引发强烈改变,累积导致皮肤萎缩和伤口愈合受损。由于担心GC可能产生永久性的不良功能变化,我们研究了长期体内暴露于GC过量是否会导致皮肤成纤维细胞持续存在缺陷。
我们研究了从患有内源性库欣综合征(CF)的患者以及性别和年龄匹配的正常供体(NF)获得的体外原代皮肤成纤维细胞培养物。研究了以下功能参数:细胞增殖、胶原蛋白分泌、基质金属蛋白酶(MMPs)及其抑制剂(金属蛋白酶组织抑制剂;TIMPs)以及收缩能力。
在不存在高皮质醇血症环境的标准培养条件下生长的CFs,与NFs相比,表现出增加的增殖能力和更高的最终细胞培养密度。在存在或不存在转化生长因子-β的情况下,胶原蛋白合成与NFs相当。然而,CFs分泌的MMP-1、MMP-2和TIMP-1水平相对较低,而TIMP-2水平几乎相等。CFs还表现出聚合胶原蛋白凝胶收缩能力增强。
总体而言,CFs的这些功能特征与已知的GC分解代谢作用相反,表明先前暴露于GC过量与成纤维细胞功能表型的持续不良结果无关。