Cardiac fibrosis is a key physiological response to cardiac tissue injury to protect the heart from wall rupture. However, its progression increases heart stiffness, eventually causing a decrease in heart contractility. Unfortunately, to date, no efficient antifibrotic therapies are available to the clinic. This is primarily due to the complexity of the process, which involves several cell types and signaling pathways. For instance, the transforming growth factor beta (TGF-β) signaling pathway has been recognized to be vital for myofibroblasts activation and fibrosis progression. In this context, complex sphingolipids, such as ganglioside GM3, have been shown to be directly involved in TGF-β receptor 1 (TGF-R1) activation. In this work, we report that an induced up-regulation of sialidase Neu3, a glycohydrolytic enzyme involved in ganglioside cell homeostasis, can significantly reduce cardiac fibrosis in primary cultures of human cardiac fibroblasts by inhibiting the TGF-β signaling pathway, ultimately decreasing collagen I deposition. These results support the notion that modulating ganglioside GM3 cell content could represent a novel therapeutic approach for cardiac fibrosis, warranting for further investigations.

中文翻译：

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唾液酸酶Neu3和神经节苷脂GM3在心脏成纤维细胞活化中的作用

心脏纤维化是对心脏组织损伤的关键生理反应，可保护心脏免于壁破裂。但是，其进展会增加心脏僵硬，最终导致心脏收缩力下降。不幸的是，迄今为止，临床上尚无有效的抗纤维化疗法。这主要是由于该过程的复杂性，它涉及几种细胞类型和信号传导途径。例如，已经公认转化生长因子β（TGF-β）信号通路对于成肌纤维细胞活化和纤维化进程至关重要。在这种情况下，复杂的鞘脂，例如神经节苷脂GM3，已被证明直接参与TGF-β受体1（TGF-R1）的激活。在这项工作中，我们报告了唾液酸酶Neu3的诱导上调，一种与神经节苷脂细胞稳态有关的糖水解酶，可以通过抑制TGF-β信号通路，最终减少胶原蛋白I的沉积，从而显着减少人心脏成纤维细胞原代培养中的心脏纤维化。这些结果支持这样的观点，即调节神经节苷脂GM3细胞含量可以代表一种用于心脏纤维化的新颖治疗方法，值得进一步研究。