Fibrosis: Sirtuins at the checkpoints of myofibroblast differentiation and profibrotic activity

Alberto Zullo, Francesco Paolo Mancini, Robert Schleip, Scott Wearing, Werner Klingler

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Fibrotic diseases are still a serious concern for public health, due to their high prevalence, complex etiology and lack of successful treatments. Fibrosis consists of excessive accumulation of extracellular matrix components. As a result, the structure and function of tissues are impaired, thus potentially leading to organ failure and death in several chronic diseases. Myofibroblasts represent the principal cellular mediators of fibrosis, due to their extracellular matrix producing activity, and originate from different types of precursor cells, such as mesenchymal cells, epithelial cells and fibroblasts. Profibrotic activation of myofibroblasts can be triggered by a variety of mechanisms, including the transforming growth factor-β signalling pathway, which is a major factor driving fibrosis. Interestingly, preclinical and clinical studies showed that fibrotic degeneration can stop and even reverse by using specific antifibrotic treatments. Increasing scientific evidence is being accumulated about the role of sirtuins in modulating the molecular pathways responsible for the onset and development of fibrotic diseases. Sirtuins are NAD+-dependent protein deacetylases that play a crucial role in several molecular pathways within the cells, many of which at the crossroad between health and disease. In this context, we will report the current knowledge supporting the role of sirtuins in the balance between healthy and diseased myofibroblast activity. In particular, we will address the signalling pathways and the molecular targets that trigger the differentiation and profibrotic activation of myofibroblasts and can be modulated by sirtuins.

Original languageEnglish
Pages (from-to)650-666
Number of pages17
JournalWound Repair and Regeneration
Volume29
Issue number4
DOIs
StatePublished - 1 Jul 2021

Keywords

  • endothelial-to-mesenchymal transition
  • epithelial-to-mesenchymal transition
  • fibroblast-to-transition
  • fibrosis
  • myofibroblast
  • myofibroblast
  • sirtuin

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