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Induction and Validation of Cellular Senescence in Primary Human Cells
08:18

Induction and Validation of Cellular Senescence in Primary Human Cells

Published on: June 20, 2018

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Molecular mechanisms for the p38-induced cellular senescence in normal human fibroblast

Gakuro Harada1, Qian Neng1, Tsukasa Fujiki1

  • 1Graduate School of Systems Life Sciences, Kyushu University, Fukuoka 812-8581, Japan and Faculty of Agriculture, Kyushu University, Fukuoka 812-8581, Japan.

Journal of Biochemistry
|June 13, 2014
PubMed

Insights

p38 MAPK activation represses human telomerase reverse transcriptase (hTERT) transcription, inducing cellular senescence in normal human cells. This finding links hTERT repression to senescence, mediated by p38 signaling pathways.

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Biochemistry

Background:

  • Transforming growth factor-beta-activated kinase 1 (TAK1), a MAP3K, represses human telomerase reverse transcriptase (hTERT) transcription and induces senescence.
  • A link between hTERT repression and cellular senescence induction was hypothesized.

Purpose of the Study:

  • To identify downstream mediators of TAK1 involved in hTERT repression and senescence.
  • To elucidate the role of p38 mitogen-activated protein kinase (MAPK) in regulating hTERT transcription and cellular senescence.

Main Methods:

  • Investigated p38 MAPK as a downstream effector of TAK1.
  • Utilized p38-specific inhibitor (SB203580) to assess p38's role in hTERT repression during senescence.
  • Employed hTERT-overexpressing and hTERT-knockdown cells to determine the necessity of hTERT repression for senescence induction.

Main Results:

  • p38 MAPK was identified as a key mediator of TAK1-induced hTERT repression.
  • hTERT expression was decreased in senescent fibroblasts and restored by p38 inhibition.
  • hTERT repression, independent of p38 activation status, is crucial for inducing cellular senescence.
  • p38 activation during serial passaging of fibroblasts leads to hTERT repression and senescence.

Conclusions:

  • p38 MAPK plays a critical role in repressing hTERT transcription and inducing cellular senescence.
  • The p38-hTERT signaling axis is a significant pathway in the process of cellular aging.
Keywords:
TAK1cellular senescencehTERThuman fibroblastp38

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