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

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Journal of Cell Communication and Signaling Aims and scope

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.

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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

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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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Correspondence to Taihao Quan.

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Quan, T., Qin, Z., Robichaud, P. et al. CCN1 contributes to skin connective tissue aging by inducing age-associated secretory phenotype in human skin dermal fibroblasts. J. Cell Commun. Signal. 5, 201–207 (2011). https://doi.org/10.1007/s12079-011-0144-0

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  • DOI: https://doi.org/10.1007/s12079-011-0144-0

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