The Yin and Yang of Integrin Function in Re-Epithelialization During Wound Healing

Background: Integrins are transmembrane proteins that are present in the plasma membrane of basal ketatinocytes and connect them to the underlying basement membrane and to the dermis. There are primarily two types of interactions between the epidermis and the dermis-via focal adhesion plaques and hemidesmosomes. It is critical that these interactions form properly to confer the skin strong mechanical properties. Integrins are also critical during wound healing, particularly in closure of the wound. The Problem: Margadant et al. (2009) address proper closure of cutaneous wounds. They developed a conditional knockout mouse for integrin alpha(3) and showed that the absence of the alpha(3) integrin resulted in faster migration of the keratinocytes during wound healing. However, its absence also led to inflammation, hair loss, basement membrane duplication, and loss of dermal epidermal interactions with blister formation. The latter has important consequences for the ability of the skin to withstand mechanical challenges. Basic/Clinical Science Advances: Models such as the conditional model developed by Margadant et al. (2009) will provide the opportunity for making major advances in understanding the complex function of integrins during healing. Clinical Care Relevance: The model and the findings provide an opportunity to decipher mechanisms of disease and for potential development of treatments for human skin disorders and impaired healing, including chronic ulcers. Conclusion: This work provides knowledge that leads to the understanding of delayed re-epithelialization during wound healing and dermal epidermal defects, blistering, and chronic skin diseases, hence providing the opportunity to understand the basic cellular and molecular mechanisms involved in these situations.