Role of sialidase Neu3 and ganglioside GM3 in cardiac fibroblasts activation: Biochemical Journal

A. Ghiroldi, M. Piccoli, P. Creo, F. Cirillo, P. Rota, S. D'Imperio, G. Ciconte, M.M. Monasky, E. Micaglio, A. Garatti, M. Aureli, E.V. Carsana, L. Menicanti, C. Pappone, L. Anastasia

Research output: Contribution to journalArticlepeer-review

Abstract

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 (TGFR1) 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).
Original languageEnglish
Pages (from-to)3401-3415
Number of pages15
JournalBiochem. J.
Volume477
Issue number17
DOIs
Publication statusPublished - 2020

Keywords

  • alpha smooth muscle actin
  • collagen type 1
  • ganglioside GM3
  • ganglioside GM3 synthase
  • messenger RNA
  • protein Neu3
  • sialidase
  • Smad2 protein
  • synthetase
  • transforming growth factor beta
  • transforming growth factor beta receptor 1
  • unclassified drug
  • Article
  • cell activation
  • collagen synthesis
  • controlled study
  • enzyme activity
  • fibroblast culture
  • gene silencing
  • heart fibroblast
  • heart muscle fibrosis
  • homeostasis
  • human
  • human cell
  • human tissue
  • mRNA expression level
  • priority journal
  • protein expression level
  • protein function
  • signal transduction
  • TGF beta signaling

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