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.
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Cover Image
Cover Image
The cover image is of a molecularly modelled receptor heterodimeric complex in its ligand bound active state (left), juxtaposed to uncomplexed receptors (right) in the presence of the proof of concept inhibitor which prevents ligand bound complex formation. For more information, see the article by Colomba and colleagues (pp. 3329–3347). The image was created by Phospho Biomedical Animation and provided by Peter Parker.
Role of sialidase Neu3 and ganglioside GM3 in cardiac fibroblasts activation
Andrea Ghiroldi, Marco Piccoli, Pasquale Creo, Federica Cirillo, Paola Rota, Sara D'Imperio, Giuseppe Ciconte, Michelle M. Monasky, Emanuele Micaglio, Andrea Garatti, Massimo Aureli, Emma Veronica Carsana, Lorenzo Menicanti, Carlo Pappone, Luigi Anastasia; Role of sialidase Neu3 and ganglioside GM3 in cardiac fibroblasts activation. Biochem J 18 September 2020; 477 (17): 3401–3415. doi: https://doi.org/10.1042/BCJ20200360
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