Springer Lactoferrin and its Role in Wound Healing

Lactoferrin is an iron-binding glycoprotein belonging to the transferrin family. It acts as a defense in host animals against microbes and viruses, since it has a broad spectrum of antimicrobial and antiviral activities. Lactoferrin has been shown to regulate the growth and differentiation of many types of cells. The results of recent studies indicate that lactoferrin is a potent regulator of dermal fibroblasts, and promotes cutaneous wound healing. The collagen gel contraction, a model of wound contraction during wound healing process, and migration of human fibroblasts were enhanced by lactoferrin. LRP-1 (LDL Receptor related Protein-1) acts as a signaling receptor for lactoferrin that mediate fibroblast response to lactoferrin by activating ERK/MAPK signaling pathway. In addition, lactoferrin promotes biosynthesis of extracellular matrix (ECM) component such as type-I collagen and hyaluronan. Hyaluronan is a major component of ECM in connective tissue and promotes wound healing. The promoting effect of lactoferrin on hyaluronan production was accompanied by promotion of HAS2 (hyaluronan synthase 2) expression. These observations suggest that lactoferrin promotes the wound healing by providing an ECM that promotes fibroblast migration. Lactoferrin is also known for its anti-inflammatory and immune modulating properties. According to recent in vivo study, lactoferrin promotes wound repair by promoting the early inflammatory phase of wound healing. Based on this, recombinant human lactoferrin was subsequently tested clinically in a Phase II trial in patients with diabetic ulcers and was found to be effective. Lactoferrin should be further evaluated in patients with diabetic and other types of ulcers. From the Back Cover “Lactoferrin and its Role in Wound Healing” summarizes the recent advances of molecular mechanisms of wound healing. It is a complex physiological process that requires the regulation of different types of cells such as immune cells, keratinocytes, fibroblasts, and endothelial cells. Lactoferrin was first identified as an iron-binding glycoprotein abundantly found in milk. It has been considered to play important roles in host defense, since lactoferrin shows broad spectrum of anti-bacterial and anti-viral activities, arising from its iron-chelating property. Furthermore, lactoferrin can regulate the function of innate and adaptive immune cells and exhibits immuno-modulating properties. These activities of lactoferrin implicate that potential use of lactoferrin as a wound healing agent. In addition, this book shows that lactoferrin is a potent regulator of dermal fibroblasts and epidermal keratinocytes, and promotes skin or corneal epithelial wound healing by increasing their proliferation, migration or deposition of extracellular matrix (ECM) components such as collagen and hyaluronan. This book provides the scientific background on use of lactoferrin as a wound healing agent. Indeed, lactoferrin exerts its biological effects by binding to specific lactoferrin receptors on target cells. This book also covers the in-depth information on roles of lactoferrin as a signaling molecule.