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α3β1 integrin in epidermis promotes wound angiogenesis and keratinocyte-to-endothelial-cell crosstalk through the induction of MRP3
Journal of Cell Science
  • Kara Mitchell, Albany Medical College
  • Charles Szekeres, Harvard Medical School
  • Vincenzo Milano, Albany Medical College
  • Kimberly B. Svenson, Albany Medical College
  • Marit Nilsen-Hamilton, Iowa State University
  • Jordan A. Kreidberg, Harvard Medical School
  • C. Michael DiPersio, Albany Medical College
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During cutaneous wound healing, epidermal keratinocytes play essential roles in the secretion of factors that promote angiogenesis. However, specific cues in the wound microenvironment that trigger the production of pro-angiogenic factors by keratinocytes, and the cellular receptors that mediate this response, remain unclear. In this study, we exploited a model of conditional integrin knockout to demonstrate impaired wound angiogenesis in mice that lack α3β1 integrin in epidermis. In addition, we used genetic and shRNA approaches to determine that α3β1-integrin deficiency in keratinocytes leads to reduced mRNA and protein expression of the pro-angiogenic factor mitogen-regulated protein 3 (MRP3; also known as PRL2C4), and to demonstrate that this regulation provides a mechanism of keratinocyte-to-endothelial-cell crosstalk that promotes endothelial-cell migration. Finally, we showed that the impaired wound angiogenesis in epidermis-specific α3-integrin-knockout mice is correlated with reduced expression of MRP3 in wounded epidermis. These findings identify a novel role for α3β1 integrin in promoting wound angiogenesis through a mechanism of crosstalk from epidermal to endothelial cells, and they implicate MRP3 in this integrin-dependent crosstalk. Such a mechanism represents a novel paradigm for integrin-mediated regulation of wound angiogenesis that extends beyond traditional roles for integrins in cell adhesion and migration.

This is an article from Journal of Cell Science 122 (2009): 1778, doi:10.1242/jcs.040956. Posted with permission.

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The Company of Biologists Limited
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Kara Mitchell, Charles Szekeres, Vincenzo Milano, Kimberly B. Svenson, et al.. "α3β1 integrin in epidermis promotes wound angiogenesis and keratinocyte-to-endothelial-cell crosstalk through the induction of MRP3" Journal of Cell Science Vol. 122 (2009) p. 1778 - 1787
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