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Molecular and cellular mechanisms of bone morphogenetic proteins and activins in the skin: potential benefits for wound healing

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Abstract

Bone morphogenetic proteins (BMPs) and activins are phylogenetically conserved proteins, belonging to the transforming growth factor-β superfamily, that signal through the phosphorylation of receptor-regulated Smad proteins, activating different cell responses. They are involved in various steps of skin morphogenesis and wound repair, as can be evidenced by the fact that their expression is increased in skin injuries. BMPs play not only a role in bone regeneration but are also involved in cartilage, tendon-like tissue and epithelial regeneration, maintain vascular integrity, capillary sprouting, proliferation/migration of endothelial cells and angiogenesis, promote neuron and dendrite formation, alter neuropeptide levels and are involved in immune response modulation, at least in animal models. On the other hand, activins are involved in wound repair through the regulation of skin and immune cell migration and differentiation, re-epithelialization and granulation tissue formation, and also promote the expression of collagens by fibroblasts and modulate scar formation. This review aims at enunciating the effects of BMPs and activins in the skin, namely in skin development, as well as in crucial phases of skin wound healing, such as inflammation, angiogenesis and repair, and will focus on the effects of these proteins on skin cells and their signaling pathways, exploring the potential therapeutic approach of the application of BMP-2, BMP-6 and activin A in chronic wounds, particularly diabetic foot ulcerations.

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Acknowledgments

This work was financially supported by Fundação para a Ciência e Tecnologia (FCT) under contract PTDC/SAU-MII/098567/2008, PEst-C/SAU/LA0001/2011 and PEst-C/SAU/LA0001/2013-2014, in addition to the EFSD/JDRF/Novo Nordisk European Programme in Type 1 Diabetes Research and Sociedade Portuguesa de Diabetologia (SPD).

Conflict of interest

The authors declare that there are no conflicts of interest.

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Authors and Affiliations

  1. Center for Neurosciences and Cell Biology, University of Coimbra, 3004-517, Coimbra, Portugal

    J. Moura, L. da Silva, M. T. Cruz & E. Carvalho

  2. Faculty of Sciences and Technology, University of Coimbra, Coimbra, Portugal

    L. da Silva

  3. Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal

    M. T. Cruz

  4. The Portuguese Diabetes Association (APDP), 1250 203, Lisbon, Portugal

    E. Carvalho

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  1. J. Moura
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  2. L. da Silva
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  3. M. T. Cruz
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  4. E. Carvalho
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Corresponding author

Correspondence to E. Carvalho.

Additional information

J. Moura and L. da Silva contributed equally to this work.

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Moura, J., da Silva, L., Cruz, M.T. et al. Molecular and cellular mechanisms of bone morphogenetic proteins and activins in the skin: potential benefits for wound healing. Arch Dermatol Res 305, 557–569 (2013). https://doi.org/10.1007/s00403-013-1381-2

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  • DOI: https://doi.org/10.1007/s00403-013-1381-2

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