Brønnum Hasse, Eskildsen Tilde, Andersen Ditte Caroline, Schneider Mikael, Sheikh Søren Paludan
Laboratory for Molecular and Cellular Cardiology, Department of Clinical Biochemistry and Pharmacology, Odense University Hospital and Institute of Molecular Medicine, University of Southern Denmark, Odense C, Denmark.
Growth Factors. 2013 Jun;31(3):81-9. doi: 10.3109/08977194.2013.787994.
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)-1β 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)-β. Therefore, we asked how IL-1β functionally modulated CF-to-myoFb differentiation. Using a differentiation model of ventricular fibroblasts, we found that IL-1β instigated substantial anti-fibrogenic effects. In specific, IL-1β reduced proliferation, matrix activity, cell motility and α-smooth muscle actin expression, which are all hallmarks of myoFb differentiation. These findings suggest that IL-1β, 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.
心脏纤维化是受损心肌的一种适应性不良反应，由分子触发因素和细胞反应之间的复杂相互作用介导。白细胞介素（IL）-1β是心脏疾病中的关键炎症诱导因子，可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。纤维化的一个主要基石是心脏成纤维细胞（CFs）向肌成纤维细胞（myoFbs）的分化，这一过程受到转化生长因子（TGF）-β的高度促进。因此，我们研究了IL-1β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-1β具有显著的抗纤维化作用。具体而言，IL-1β降低了增殖、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-1β除了在炎症反应中具有公认的不良作用外，还可以通过积极抑制CF向纤维化myoFb的分化，在心脏纤维化中发挥有益作用。
