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Spatiotemporal expression of periostin during skin development and incisional wound healing: lessons for human fibrotic scar formation

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Journal of Cell Communication and Signaling Aims and scope

Abstract

Differentiation of fibroblasts to myofibroblasts and collagen fibrillogenesis are two processes essential for normal cutaneous development and repair, but their misregulation also underlies skin-associated fibrosis. Periostin is a matricellular protein normally expressed in adult skin, but its role in skin organogenesis, incisional wound healing and skin pathology has yet to be investigated in any depth. Using C57/BL6 mouse skin as model, we first investigated periostin protein and mRNA spatiotemporal expression and distribution during development and after incisional wounding. Secondarily we assessed whether periostin is expressed in human skin pathologies, including keloid and hypertrophic scars, psoriasis and atopic dermatitis. During development, periostin is expressed in the dermis, basement membrane and hair follicles from embryonic through neonatal stages and in the dermis and hair follicle only in adult. In situ hybridization demonstrated that dermal fibroblasts and basal keratinocytes express periostin mRNA. After incisional wounding, periostin becomes re-expressed in the basement membrane within the dermal-epidermal junction at the wound edge re-establishing the embryonic deposition pattern present in the adult. Analysis of periostin expression in human pathologies demonstrated that it is over-expressed in keloid and hypertrophic scars, atopic dermatitis, but is largely absent from sites of inflammation and inflammatory conditions such as psoriasis. Furthermore, in vitro we demonstrated that periostin is a transforming growth factor beta 1 inducible gene in human dermal fibroblasts. We conclude that periostin is an important ECM component during development, in wound healing and is strongly associated with pathological skin remodeling.

Summary: Periostin is a fibrogenic protein that mediates fibroblast differentiation and extracellular matrix synthesis. Here, we show that periostin is dynamically and temporally expressed during skin development, is induced by TGF-β1 in vitro and is significantly upregulated during wound repair as well as cutaneous pathologies.

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Abbreviations

BM:

Basement membrane

DEJ:

Dermal-epidermal junction

E:

Embryonic

ECM:

Extracellular matrix

HF:

Hair follicle

ISH:

In situ hybridization

P:

Postnatal

SB:

Subcutaneous tissue

TGF-β:

Transforming growth factor beta

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Acknowledgments

We thank Prof. Jeffery B. Travers (Departments of Dermatology and Pediatrics, IUPUI) for providing the fixed skin biopsy specimens and Linda Jackson-Boeters (Department of Pathology, UWO) for advice on histological analysis. This work was supported, in part, by the National Institutes of Health (S.J.C), the IU Department of Pediatrics (Cardiology) and Riley Children’s Foundation (H-M.Z), Natural Sciences and Engineering Research Council (C.E) and the Canadian Institutes of Health Research IMHA operating grants (D.W.H).

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Authors and Affiliations

  1. Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, 46202, USA

    Hong-Ming Zhou, Jian Wang & Simon J. Conway

  2. Division of Oral Biology and Anatomy & Cell Biology, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, Ontario, N6A 5C1, Canada

    Christopher Elliott, Weiyan Wen & Douglas W. Hamilton

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  1. Hong-Ming Zhou
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  2. Jian Wang
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  3. Christopher Elliott
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  4. Weiyan Wen
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  5. Douglas W. Hamilton
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  6. Simon J. Conway
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Correspondence to Douglas W. Hamilton or Simon J. Conway.

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Zhou, HM., Wang, J., Elliott, C. et al. Spatiotemporal expression of periostin during skin development and incisional wound healing: lessons for human fibrotic scar formation. J. Cell Commun. Signal. 4, 99–107 (2010). https://doi.org/10.1007/s12079-010-0090-2

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