Influence of the extracellular matrix on cell-intrinsic circadian clocks

J Cell Sci. 2019 Feb 1;132(3):jcs207498. doi: 10.1242/jcs.207498.

Abstract

Cell-autonomous circadian clocks coordinate tissue homeostasis with a 24-hourly rhythm. The molecular circadian clock machinery controls tissue- and cell type-specific sets of rhythmic genes. Disruptions of clock mechanisms are linked to an increased risk of acquiring diseases, especially those associated with aging, metabolic dysfunction and cancer. Despite rapid advances in understanding the cyclic outputs of different tissue clocks, less is known about how the clocks adapt to their local niche within tissues. We have discovered that tissue stiffness regulates circadian clocks, and that this occurs in a cell-type-dependent manner. In this Review, we summarise new work linking the extracellular matrix with differential control of circadian clocks. We discuss how the changes in tissue structure and cellular microenvironment that occur throughout life may impact on the molecular control of circadian cycles. We also consider how altered clocks may have downstream impacts on the acquisition of diseases.

Keywords: Breast; Circadian clock; Circadian gene expression; Epidermis; Epithelial cell; Fibroblast; Lung.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • ARNTL Transcription Factors / genetics
  • ARNTL Transcription Factors / metabolism
  • Animals
  • CLOCK Proteins / genetics
  • CLOCK Proteins / metabolism
  • Cellular Microenvironment / genetics
  • Circadian Clocks / genetics*
  • Circadian Rhythm / genetics*
  • Cryptochromes / genetics
  • Cryptochromes / metabolism
  • Eukaryotic Cells / cytology
  • Eukaryotic Cells / metabolism
  • Extracellular Matrix / chemistry
  • Extracellular Matrix / metabolism*
  • Feedback, Physiological*
  • Gene Expression Regulation*
  • Homeostasis / genetics
  • Humans
  • Mammals
  • Mechanotransduction, Cellular*
  • Period Circadian Proteins / genetics
  • Period Circadian Proteins / metabolism
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism

Substances

  • ARNTL Transcription Factors
  • BMAL1 protein, human
  • CRY1 protein, human
  • Cryptochromes
  • PER1 protein, human
  • Period Circadian Proteins
  • Protein Isoforms
  • CLOCK Proteins
  • CLOCK protein, human