IL-1β suppresses TGF-β-mediated myofibroblast differentiation in cardiac fibroblasts
IL-1β suppresses TGF-β-mediated myofibroblast differentiation in cardiac fibroblasts
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DOI：
10.3109/08977194.2013.787994
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发表时间：
2013-06-01
期刊：
影响因子：
1.8
通讯作者：
Sheikh, Soren Paludan
中科院分区：
文献类型：
--
作者：
Bronnum, Hasse;Eskildsen, Tilde;Sheikh, Soren Paludan
心脏纤维化是受损心肌的适应不良反应，并通过分子触发物和细胞反应之间的复杂相互作用介导。白细胞介素（IL）-1 β是心脏疾病中的关键炎症诱导物，并促进细胞侵袭和心肌细胞损伤，但其对纤维化的影响知之甚少。纤维化的主要基石是心脏成纤维细胞（CF）分化成肌成纤维细胞（myoFbs），其由转化生长因子（TGF）-β高度促进。因此，我们研究了IL-1 β如何在功能上调节CF向myoFb的分化。使用心室成纤维细胞的分化模型，我们发现IL-1 β激发了实质性的抗纤维化作用。具体而言，IL-1 β降低增殖、基质活性、细胞运动性和α-平滑肌肌动蛋白表达，这些都是myoFb分化的标志。这些发现表明，IL-1 β，除了其公认的不利作用，在炎症反应，也可以发挥有益的影响，在心脏纤维化的积极抑制分化的CF成纤维化的肌纤维。
Cardiac fibrosis is a maladaptive response of the injured myocardium and is mediated through a complex interplay between molecular triggers and cellular responses. Interleukin (IL)-1 beta is a key inflammatory inducer in cardiac disease and promotes cell invasion and cardiomyocyte injury, but little is known of its impact on fibrosis. A major cornerstone of fibrosis is the differentiation of cardiac fibroblasts (CFs) into myofibroblasts (myoFbs), which is highly promoted by Transforming Growth Factor (TGF)-beta. Therefore, we asked how IL-1 beta functionally modulated CF-to-myoFb differentiation. Using a differentiation model of ventricular fibroblasts, we found that IL-1 beta instigated substantial anti-fibrogenic effects. In specific, IL-1 beta reduced proliferation, matrix activity, cell motility and a-smooth muscle actin expression, which are all hallmarks of myoFb differentiation. These findings suggest that IL-1 beta, besides from its acknowledged adverse role in the inflammatory response, can also exert beneficial effects in cardiac fibrosis by actively suppressing differentiation of CFs into fibrogenic myoFbs.