Insulin-like growth factors (IGF) and IGF-binding proteins bound to vitronectin enhance keratinocyte protein synthesis and migration.
The insulin-like growth factor (IGF) system plays an important role in a number of disease states, such as cancer and psoriasis, through its ability to modulate cell proliferation, attachment, and migration. The type-1 IGF and type-2 IGF receptors, as well as six IGF-binding proteins (IGFBP-1-6), have well-established roles in mediating IGF activity. Additionally, it's been demonstrated that IGF-II binds directly to the extracellular matrix protein vitronectin (VN), whereas IGF-I does not. IGFBP-5, however, has been recently demonstrated to facilitate the binding of IGF-I to VN. The aim of this study was to determine whether the interaction between IGF, IGFBP, and VN modulates human keratinocyte function. Functional assays demonstrated that both the IGF-II:VN and IGF-I:IGFBP-5:VN complexes resulted in significantly enhanced protein synthesis and cell migration through 12 microm pore Transwells in skin keratinocytes (HaCAT). Furthermore, the IGF-II:VN complex significantly enhanced human corneal epithelial (HCE) cell protein synthesis. Interestingly, the IGF-II:VN complex did not effect either HCE cell migration or attachment. This is the first study to demonstrate a functional role for the interaction between IGF and VN in human keratinocytes. Moreover, these results suggest that IGF-II:VN and IGF-I:IGFBP-5:VN complexes may be useful in situations where enhanced keratinocyte cell migration and proliferation is required, such as in wound healing and skin regeneration.
Hyde
Carolyn
C
Tissue BioRegeneration and Integration Program, Science Research Center, School of Life Sciences, Queensland University of Technology, Brisbane, Qld 4000, Australia. ce.hyde@student.qut.edu.au
Hollier
Brett
B
Anderson
Alex
A
Harkin
Damien
D
Upton
Zee
Z
D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D019281:Dimerization; D006801:Humans; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D007335:Insulin-Like Growth Factor II / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D014176:Protein Biosynthesis; D019096:Vitronectin / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D014945:Wound Healing / Q000502:physiology
D018975:Insulin-Like Growth Factor Binding Protein 5; D019096:Vitronectin; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II