microRNA-dependent regulation of biomechanical genes establishes tissue stiffness homeostasis

Research output: Contribution to journalArticle

  • External authors:
  • Albertomaria Moro
  • Tristan Driscoll
  • William Amero
  • Liana Borass
  • Dionna Kaspar
  • Nicolas Baeyens
  • Charlene Jouy
  • Venkatesh Mallikarjun
  • Sang Joon Ahn
  • Donghoon Lee
  • Jing Zhang
  • Mengting Gu
  • Mark Gerstein
  • Stefania Nicoli

Abstract

The mechanical properties of tissues, which are determined primarily by their extracellular matrix (ECM), are largely stable over time despite continual turnover of ECM constituents 1,2. These observations imply active homeostasis, where cells sense and adjust rates of matrix synthesis, assembly and degradation to keep matrix and tissue properties within the optimal range. However, the regulatory pathways that mediate this process are essentially unknown3. Genome-wide analyses of endothelial cells revealed abundant microRNA-mediated regulation of cytoskeletal, adhesive and extracellular matrix (CAM) mRNAs. High-throughput assays showed co-transcriptional regulation of microRNA and CAM genes on stiff substrates, which buffers CAM expression. Disruption of global or individual microRNA-dependent suppression of CAM genes induced hyper-adhesive, hyper-contractile phenotypes in multiple systems in vitro, and increased tissue stiffness in the zebrafish fin-fold during homeostasis and regeneration in vivo. Thus, a network of microRNAs and CAM mRNAs mediate tissue mechanical homeostasis.

Bibliographical metadata

Original languageEnglish
Article numberNCB-N34535E
JournalNature Cell Biology
Early online date11 Feb 2019
DOIs
Publication statusPublished - 2019

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