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Journal of Cell Communication and Signaling

, Volume 5, Issue 3, pp 201–207 | Cite as

CCN1 contributes to skin connective tissue aging by inducing age-associated secretory phenotype in human skin dermal fibroblasts

  • Taihao Quan
  • Zhaoping Qin
  • Patrick Robichaud
  • John J. Voorhees
  • Gary J. Fisher
Research Article

Abstract

Dermal connective tissue collagen is the major structural protein in skin. Fibroblasts within the dermis are largely responsible for collagen production and turnover. We have previously reported that dermal fibroblasts, in aged human skin in vivo, express elevated levels of CCN1, and that CCN1 negatively regulates collagen homeostasis by suppressing collagen synthesis and increasing collagen degradation (Quan et al. Am J Pathol 169:482–90, 2006, J Invest Dermatol 130:1697–706, 2010). In further investigations of CCN1 actions, we find that CCN1 alters collagen homeostasis by promoting expression of specific secreted proteins, which include matrix metalloproteinases and proinflammatory cytokines. We also find that CCN1-induced secretory proteins are elevated in aged human skin in vivo. We propose that CCN1 induces an “Age-Associated Secretory Phenotype”, in dermal fibroblasts, which mediates collagen reduction and fragmentation in aged human skin.

Keywords

CCN1 Age-associated secretory phenotype Skin connective tissue aging 

Abbreviations

CCN1

cysteine-rich protein 61

CCN family

cysteine-rich protein 61, connective tissue growth factor, nephroblastoma overexpressed

AFM

atomic force microscopy

MMP

matrix metalloproteinases

ECM

extracellular matrix

PCR

polymerase chain reaction

IL

interleukin

NF-κB

nuclear factor kappa B

Notes

Acknowledgments

We thank Suzan Rehbine for the procurement of tissue specimens, and Diane Fiolek for graphic and administrative assistance. This work was supported by the National Institute of Health (ES014697 and ES014697 30S1 to T Quan; AG019364 and AG025186 to G Fisher).

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Copyright information

© The International CCN Society 2011

Authors and Affiliations

  • Taihao Quan
    • 1
  • Zhaoping Qin
    • 1
  • Patrick Robichaud
    • 1
  • John J. Voorhees
    • 1
  • Gary J. Fisher
    • 1
  1. 1.Department of DermatologyUniversity of Michigan Medical SchoolAnn ArborUSA

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