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Reduced expression of connective tissue growth factor (CTGF/CCN2) mediates collagen loss in chronologically aged

TaiHao Quan1, Yuan Shao, Tianyuan He

  • 1Department of Dermatology, University of Michigan, Ann Arbor, Michigan 48109-5609, USA.

The Journal of Investigative Dermatology
|July 31, 2009
PubMed

Insights

Aging reduces collagen production in human skin due to a weakened transforming growth factor-beta (TGF-beta)/Smad/connective tissue growth factor (CTGF) pathway. This axis is crucial for maintaining collagen levels in dermal fibroblasts.

Area of Science:

  • Dermatology
  • Cell Biology
  • Molecular Biology

Background:

  • Chronological aging in human skin is characterized by reduced type I procollagen production.
  • Connective tissue growth factor (CTGF/CCN2) is a key mediator in fibrotic disorders, typically stimulating collagen production.
  • CTGF is constitutively expressed in normal dermis, suggesting a physiological role in collagen regulation.

Purpose of the Study:

  • To investigate the role of the transforming growth factor-beta (TGF-beta)/Smad/CTGF axis in aged human skin.
  • To determine the impact of TGF-beta and CTGF on type I procollagen expression in dermal fibroblasts.

Main Methods:

  • Analysis of the TGF-beta/Smad/CTGF axis in dermal fibroblasts from aged (≥80 years) versus younger human skin.
  • Experimental manipulation of TGF-beta and CTGF levels (neutralization, knockdown, overexpression) in primary human skin fibroblasts.
  • Assessment of type I procollagen mRNA, protein, and promoter activity.
  • Investigation of downstream signaling pathways including Smad phosphorylation and transcriptional activity.

Main Results:

  • The TGF-beta/Smad/CTGF axis is significantly downregulated in dermal fibroblasts from aged human skin.
  • Neutralization of TGF-beta or CTGF knockdown reduced type I procollagen expression.
  • CTGF overexpression increased type I procollagen expression and promoter activity.
  • Inhibition of TGF-beta receptor kinase, Smad4 knockdown, or Smad7 overexpression abolished CTGF-induced procollagen expression, but CTGF did not affect Smad3 phosphorylation.

Conclusions:

  • Type I procollagen expression in human skin fibroblasts is dependent on both TGF-beta and CTGF, acting via interconnected but distinct mechanisms.
  • Downregulation of the TGF-beta/Smad/CTGF axis contributes to the reduced type I procollagen synthesis observed in aged skin.

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