Epidermal Differentiation in Barrier Maintenance and Wound Healing

Abstract

Significance: The epidermal barrier prevents water loss and serves as the body's first line of defense against toxins, chemicals, and infectious microbes. Disruption of the barrier, either through congenital disorders of barrier formation or through wounds, puts the individual at risk for dehydration, hypersensitivity, infection, and prolonged inflammation. Epidermal barrier disorders affect millions of patients in the United States, causing loss of productivity and diminished quality of life for patients and their families, and represent a burden to the health-care system and society. Recent Advances: The genetic basis of many congenital barrier disorders has been identified in recent years, and great advances have been made in the molecular mechanisms of the formation and homeostasis of epidermal barrier, as well as acute and chronic wound healing. Progress in stem cell (SC) biology, particularly in induced pluripotent stem cells (iPSCs) and allogeneic mesenchymal stem cells (MSCs), has opened new doors for cell-based therapy of chronic wounds. Critical Issues: Understanding of the molecular mechanisms of barrier homeostasis in health and disease, as well as contributions of iPSCs and allogeneic MSCs to wound healing, will lead to the identification of novel targets for developing therapeutics for congenital barrier and wound healing disorders. Future Directions: Future studies should focus on better understanding of molecular mechanisms leading to disrupted homeostasis of epidermal barrier to identify potential therapeutic targets to combat its associated diseases.

Tongyu Cao Wikramanayake, PhD

Figure 1.

Schematic diagram of epidermal differentiation. Differentiation specific keratins K1, K10, K2e, and K9 are expressed in differentiating cells of suprabasal epidermal layers. To see this illustration in color, the reader is referred to the web version of this article at www.liebertpub.com/wound

Figure 2.

Conserved expression of epidermal differentiation marker genes between the murine and human skin despite the differences in morphology. Basal keratinocytes express keratin 5 and keratin 14, and differentiation-specific markers, filaggrin and keratin 10, are expressed in suprabasal layers of murine as well as in human skin. Scale bar, 100 μm. To see this illustration in color, the reader is referred to the web version of this article at www.liebertpub.com/wound