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Spatial-temporal modulation of CCN proteins during wound healing in human skin in vivo

Journal of Cell Communication and Signaling volume 5, pages 69–80 (2011)Cite this article

Abstract

CCN proteins are important modulators of development and function of adult organs. In this study, we examined the localization and expression of the six CCN family members in normal adult human skin and during wound healing in vivo. Transcript and protein expression were studied by laser-capture microdissection-coupled real-time PCR and immunohistochemistry, respectively. Our results demonstrate that CCN1, CCN4, and CCN6 are expressed at relatively low levels in normal human skin. CCN2, CCN3, and CCN5 are the most highly expressed transcripts in the epidermis. CCN3 and CCN5 proteins are prominent in epidermal keratinocytes, whereas CCN2 is primarily expressed in melanocytes. Differential expression within epidermal layers suggests that CCN3 and CCN5 are linked with keratinocyte differentiation. CCN2, CCN3 and CCN5, are the three most highly expressed transcripts in the dermis. Their respective proteins are produced to various extents by dermal fibroblasts, blood vessels, eccrine sweat glands and hair follicles. We find that most CCN family members are temporally and specifically regulated during different phases (inflammation, proliferation, and remodeling) of partial thickness wound repair. By highlighting spatial-temporal regulations of CCN family member expression in relation to cell proliferation and differentiation, our results suggest a diverse range of functions for CCN proteins in both epidermal and dermal cells, and provides a solid reference for interpretation of future studies aimed at understanding the role of CCN proteins in human skin physiology and diseases.

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Abbreviations

ECM:

Extracellular matrix

qPCR:

Quantitative real-time RT-PCR

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Acknowledgements

We would like to thank Suzan Rehbine, LPN, for her help with volunteer recruitment and procurement of biopsies. We would also like to thank Trupta Purohit for helpful discussions, and Monica Michelotti for technical help with antibody titrations. BP wishes to thank GJ Fisher for hosting while on leave from Université Paris 7.

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Author notes

  1. Bernard Perbal

    Present address: Direction des Sciences du Vivant, L’Oréal Recherche et Innovation, Clichy, France

Affiliations

  1. Department of Dermatology, University of Michigan, Medical Science Building I, Rm 6447, 1301 E. Catherine, Ann Arbor, MI, 48109, USA

    Laure Rittié

  2. Department of Dermatology, University of Michigan, Ann Arbor, MI, USA

    Bernard Perbal, Jeffrey S. Orringer, John J. Voorhees & Gary J. Fisher

  3. Laboratoire d’ Oncologie Virale et Moléculaire, Université Paris 7 - D. Diderot, Paris, France

    Bernard Perbal

  4. Department of Anatomy & Cellular Biology, Tufts University, Boston, MA, USA

    John J. Castellot Jr.

Authors
  1. Laure Rittié
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  2. Bernard Perbal
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  3. John J. Castellot Jr.
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  4. Jeffrey S. Orringer
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  5. John J. Voorhees
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Correspondence to Laure Rittié.

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Rittié, L., Perbal, B., Castellot, J.J. et al. Spatial-temporal modulation of CCN proteins during wound healing in human skin in vivo. J. Cell Commun. Signal. 5, 69–80 (2011). https://doi.org/10.1007/s12079-010-0114-y

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  • DOI: https://doi.org/10.1007/s12079-010-0114-y

Keywords

  • CCN
  • Inflammation
  • Remodeling
  • Skin
  • Wound
  • Extracellular matrix