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AGE

, Volume 36, Issue 1, pp 353–364 | Cite as

Elevated cysteine-rich protein 61 (CCN1) promotes skin aging via upregulation of IL-1β in chronically sun-exposed human skin

  • Zhaoping Qin
  • Toru Okubo
  • John J. Voorhees
  • Gary J. Fisher
  • Taihao Quan
Article

Abstract

Chronic exposure of human skin to solar ultraviolet (UV) irradiation causes premature skin aging, which is characterized by reduced type I collagen production and increased fragmentation of the dermal collagenous extracellular matrix. This imbalance of collagen homeostasis is mediated, in part, by elevated expression of the matricellular protein cysteine-rich protein 61 (CCN1), in dermal fibroblasts, the primary collagen producing cell type in human skin. Here, we report that the actions of CCN1 are mediated by induction of interleukin 1β (IL-1β). CCN1 and IL-1β are strikingly induced by acute UV irradiation, and constitutively elevated in sun-exposed prematurely aged human skin. Elevated CCN1 rapidly induces IL-1β, inhibits type I collagen production, and upregulates matrix metalloproteinase-1, which degrades collagen fibrils. Blockade of IL-1β actions by IL-1 receptor antagonist largely prevents the deleterious effects of CCN1 on collagen homeostasis. Furthermore, knockdown of CCN1 significantly reduces induction of IL-1β by UV irradiation, and thereby partially prevents collagen loss. These data demonstrate that elevated CCN1promotes inflammaging and collagen loss via induction of IL-1β and thereby contributes to the pathophysiology of premature aging in chronically sun-exposed human skin.

Keywords

Inflammaging CCN1 IL-1β Collagen homeostasis Fibroblasts 

Abbreviations

UV

Ultraviolet

CCN1

CCN family member 1

CCN family

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

IL-1β

Interleukin 1β

COL-1

Type I collagen

MMP-1

Matrix metalloproteinase-1

ECM

Extracellular matrix

AFM

Atomic force microscopy

AP-1

Activator protein-1

NF-κB

Nuclear factor kappa B

Notes

Acknowledgments

We thank Suzan Rehbine for the procurement of tissue specimens, and Diane Fiolek and Patrick Robichaud for administrative assistance. This work was supported by the National Institute of Health (RO1 ES014697 and ES014697 30S1 to T. Quan).

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Copyright information

© American Aging Association 2013

Authors and Affiliations

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

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