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Downregulation of activin-signaling gene expression in passaged normal human dermal fibroblasts

Young Il Kim1, Chan-Yang Lee2, Min Kyung Shin2

  • 1Medical Science Research Institute, Kyung Hee University Medical Center, Seoul 02447, Republic of Korea.

Biomedical Reports
|December 17, 2019
PubMed

Insights

As human dermal fibroblasts age, levels of activin A and follistatin increase, while activin receptor-Smad signaling pathways decrease, impacting cell functions.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Dermatology

Background:

  • Activins, part of the transforming growth factor-β (TGF-β) superfamily, regulate crucial cellular processes like proliferation, differentiation, and apoptosis.
  • Understanding how aging affects these signaling pathways in fibroblasts is vital for regenerative medicine and aging research.

Purpose of the Study:

  • To investigate the changes in activin, activin receptor (ActR), and Smad-signaling gene expression in normal human dermal fibroblasts as they age (increase in passage number).

Main Methods:

  • Gene and protein expression levels were quantified using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunoblot analysis.
  • Experiments were conducted on normal human dermal fibroblasts across passage numbers 5 to 15.

Main Results:

  • Activin A and follistatin mRNA levels showed an increase with higher passage numbers.
  • Expression of ActR types IA, IB, IIA, and IIB mRNA decreased in aged fibroblasts.
  • Smad2, Smad3, and Smad4 protein levels diminished, alongside reduced phosphorylation of Smad2 and Smad3, while Smad7 expression was enhanced in older cells.

Conclusions:

  • Aging in normal human dermal fibroblasts leads to an upregulation of activin A and follistatin.
  • The study indicates a downregulation of the activin receptor-Smad signaling pathway in aging fibroblasts, suggesting a shift in cellular response mechanisms.
Keywords:
Smadactivinactivin receptorfibroblastfollistatin

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