Transcriptional noise in intact and TGF-beta treated human kidney cells; the importance of time-series designs

Cell Biol Int. 2018 Sep;42(9):1265-1269. doi: 10.1002/cbin.10992. Epub 2018 Jun 15.

Abstract

The transforming growth factor (TGF)-β signaling pathway plays a key role in various cellular processes. However, insufficient knowledge about the complex and sometimes paradoxical functions of this pathway hinders its therapeutic targeting. In this study, the transcriptional profile of seven mediators and downstream elements of the TGF-β pathway were assessed in TGF-β treated and untreated human kidney derived cells for 2 weeks in a time course manner. As expected the up-regulation of ACTA2 and COL1A2 was evident in the treated cells. However, we observed remarkable fluctuations in gene expression, even in the supposedly steady states. The magnitude of noise was diverse in the examined genes. Our findings underscore the significance of time-course designs for gene expression analyses and clearly show that misleading data can be obtained in single point measurements. Furthermore, we propose specific considerations in the interpretation of time-course data in the context of noisy gene expression.

Keywords: gene expression analysis; signal transduction; time-series design; transcriptional noise; transforming growth factor-β.

MeSH terms

  • Actins / drug effects
  • Cells, Cultured
  • Collagen / metabolism
  • Collagen Type I / drug effects
  • Collagen Type I / metabolism
  • Fibroblasts / metabolism
  • Gene Expression / genetics
  • Humans
  • Kidney / metabolism
  • Signal Transduction / genetics
  • Signal-To-Noise Ratio*
  • Smad3 Protein / metabolism
  • Time Factors
  • Trans-Activators / metabolism
  • Transcription, Genetic / genetics
  • Transcription, Genetic / physiology
  • Transcriptional Activation / genetics*
  • Transcriptional Activation / physiology
  • Transforming Growth Factor beta / metabolism*
  • Transforming Growth Factor beta1 / metabolism
  • Up-Regulation

Substances

  • ACTA2 protein, human
  • Actins
  • COL1A2 protein, human
  • Collagen Type I
  • Smad3 Protein
  • Trans-Activators
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • Collagen