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Epitranscriptomics in fibroblasts and fibrosis.

Mirolyuba Ilieva1, Shizuka Uchida1

  • 1Center for RNA Medicine, Department of Clinical Medicine, Aalborg University, Copenhagen, Denmark.

American Journal of Physiology. Cell Physiology
|May 4, 2022
PubMed
Summary
This summary is machine-generated.

Fibroblast-associated fibrosis is modulated by epitranscriptomic marks like RNA methylation and editing. Understanding these RNA modifications offers new therapeutic targets for fibrotic diseases.

Keywords:
RNA editingRNA methylationepitranscriptomicsfibroblastfibrosis

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Area of Science:

  • Molecular Biology
  • Epigenetics
  • Pathology

Background:

  • Fibroblasts are key players in fibrotic diseases affecting organs like lungs, heart, liver, skin, and kidneys.
  • The epitranscriptome, encompassing over 170 RNA modifications, is increasingly recognized for its role in modulating fibrosis.
  • Recent advancements in high-throughput technologies enable detailed investigation of RNA modification sites and their mechanisms in fibrosis.

Purpose of the Study:

  • To review the latest research on epitranscriptomic modifications in fibroblast biology and fibrosis.
  • To highlight the involvement of specific RNA modifications, including N6-adenosine methylation, A-to-I RNA editing, and 5-methylcytosine, in fibrotic processes.
  • To elucidate future research directions for targeting epitranscriptomic alterations in fibrotic diseases.

Main Methods:

  • Review of current literature on epitranscriptomics and fibrosis.
  • Focus on high-throughput methods for identifying RNA modification sites and their functions.
  • Analysis of mechanisms involving key epitranscriptomic regulators such as METTL3/14/16, FTO, ALKBH5, and ADAR proteins.

Main Results:

  • N6-adenosine methylation, A-to-I RNA editing, and 5-methylcytosine are prevalent RNA modifications found in mRNA, pre-mRNA, and ncRNAs.
  • These modifications have been observed to influence fibroblast behavior and contribute to fibrosis in various experimental models.
  • Specific enzymes and proteins involved in RNA modification (e.g., METTL3, FTO, ADAR) play critical roles in the pathogenesis of fibrosis.

Conclusions:

  • Epitranscriptomic modifications are significant modulators of fibroblast function and fibrotic disease progression.
  • Targeting RNA modifications presents a promising avenue for developing novel therapeutic strategies against fibrosis.
  • Further research is warranted to fully understand the intricate roles of epitranscriptomic marks in fibrosis and to translate these findings into clinical applications.