Lactoferrin promotes collagen gel contractile activity of fibroblasts mediated by lipoprotein receptors.
Lactoferrin is an iron-binding glycoprotein that belongs to the transferrin family. Recent studies in vitro and in vivo suggest that lactoferrin is a potential therapeutic agent for wound healing. We have shown that both bovine and human lactoferrin enhance the collagen gel contractile activity of WI-38 human fibroblasts. The collagen gel contraction is considered as an in vitro model for reorganization of the collagen matrix during the wound healing process. The elevation of collagen gel contractile activity induced by lactoferrin was accompanied by activation of extracellular-regulated kinase (ERK) 1/2 and myosin light chain kinase (MLCK), and subsequent elevation of myosin light chain (MLC) phosphorylation. The effects of lactoferrin on collagen gel contraction and the activation of the signaling pathway were dependent on the expression of low-density lipoprotein receptor - related protein (LRP) - 1 in the fibroblasts. LRP-1 is known as an endocytosis receptor and is involved in the cellular uptake of diverse ligands, including lactoferrin. In addition, LRP-1 acts as a signaling lactoferrin receptor in mammalian cells by converting the lactoferrin-binding signal into the activation of the intracellular signaling pathway. This property was found to be independent of the endocytic function of LRP-1, as seen in osteoblast-like cells.
Takayama
Yoshiharu
Y
Functional Bio-molecules Laboratory, National Institute of Livestock and Grassland Science, Tsukuba, Ibaraki, 305-0901, Japan. takay@affrc.go.jp
Takezawa
Toshiaki
T
D000818:Animals; D002465:Cell Movement; D003094:Collagen / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007781:Lactoferrin / Q000378:metabolism* / Q000494:pharmacology; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000378:metabolism*; D015398:Signal Transduction; D014945:Wound Healing / Q000502:physiology
D026503:Low Density Lipoprotein Receptor-Related Protein-1; D003094:Collagen; D007781:Lactoferrin