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Tytuł:
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Role of sialidase Neu3 and ganglioside GM3 in cardiac fibroblasts activation.
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Autorzy:
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Ghiroldi A; Laboratory of Stem Cells for Tissue Engineering, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy.
Piccoli M; Laboratory of Stem Cells for Tissue Engineering, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy.
Creo P; Laboratory of Stem Cells for Tissue Engineering, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy.
Cirillo F; Laboratory of Stem Cells for Tissue Engineering, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy.
Rota P; Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy.
D'Imperio S; Laboratory of Stem Cells for Tissue Engineering, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy.; Department of Biomedical Sciences for Health, University of Milan, Milan, Italy.; Arrhythmology Department, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy.
Ciconte G; Arrhythmology Department, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy.
Monasky MM; Arrhythmology Department, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy.
Micaglio E; Arrhythmology Department, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy.
Garatti A; Department of Cardiovascular Disease 'E. Malan', Cardiac Surgery Unit, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy.
Aureli M; Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy.
Carsana EV; Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy.
Menicanti L; Department of Cardiovascular Disease 'E. Malan', Cardiac Surgery Unit, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy.
Pappone C; Arrhythmology Department, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy.; University of Vita-Salute San Raffaele, Milan, Italy.
Anastasia L; Laboratory of Stem Cells for Tissue Engineering, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy.; University of Vita-Salute San Raffaele, Milan, Italy.
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Źródło:
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The Biochemical journal [Biochem J] 2020 Sep 18; Vol. 477 (17), pp. 3401-3415.
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Typ publikacji:
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Journal Article; Research Support, Non-U.S. Gov't
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Język:
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English
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Imprint Name(s):
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Original Publication: London, UK : Published by Portland Press on behalf of the Biochemical Society
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MeSH Terms:
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Gene Expression Regulation, Enzymologic*
Up-Regulation*
Fibroblasts/*metabolism
G(M3) Ganglioside/*metabolism
Myocardium/*metabolism
Neuraminidase/*biosynthesis
Fibroblasts/pathology ; Fibrosis ; Humans ; Myocardium/pathology ; Receptor, Transforming Growth Factor-beta Type I/metabolism
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Contributed Indexing:
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Keywords: cardiac fibroblasts; fibrosis; sialidase Neu3; sphingolipids
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Substance Nomenclature:
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0 (G(M3) Ganglioside)
EC 2.7.11.30 (Receptor, Transforming Growth Factor-beta Type I)
EC 2.7.11.30 (TGFBR1 protein, human)
EC 3.2.1.18 (Neu3 protein, human)
EC 3.2.1.18 (Neuraminidase)
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Entry Date(s):
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Date Created: 20200902 Date Completed: 20210222 Latest Revision: 20210222
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Update Code:
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20240104
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DOI:
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10.1042/BCJ20200360
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PMID:
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32869836
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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.
(© 2020 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)