Migration of keratinocytes is impaired on glycated collagen I.
Advanced glycation end products are the chemical modification of proteins induced by sugars in a hyperglycemic condition. Extracellular matrix proteins are prominent targets of nonenzymatic glycation because of their slow turnover rates. The aim of this study was to investigate the influence of nonenzymatic glycation of type I collagen on the migration of keratinocytes. The migration of keratinocytes was dramatically promoted on native type I collagen-coated dishes compared with that on uncoated dishes. When type I collagen was glycated with glycolaldehyde, large amounts of advanced glycation end products were produced; the glycated collagen I-coated dishes did not promote the migration of keratinocytes. Glycated collagen I did not affect the proliferative capacity of keratinocytes. However, the adhesion of keratinocytes to glycated collagen I was profoundly diminished in a glycation intensity-dependent manner. alpha2beta1 integrin is responsible for the migration and adhesion of keratinocytes to type I collagen. Pretreatment with glycated collagen I did not affect the expression level or functional activity of alpha2beta1 integrin on keratinocytes. These findings suggest that in the presence of glycated collagen I, keratinocytes lose their adhesive and migratory abilities. As the glycation did not modify the alpha2beta1 integrin on keratinocytes, it is suggested that glycation may diminish the binding capacity of type I collagen.
Morita
Keisuke
K
Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. kmorita@dermatol.med.kyushu-u.ac.jp
Urabe
Kazunori
K
Moroi
Yoichi
Y
Koga
Tetsuya
T
Nagai
Ryuji
R
Horiuchi
Seiko
S
Furue
Masutaka
M
D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000378:metabolism / Q000503:physiopathology; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D015603:Keratinocytes / Q000502:physiology*
D024042:Collagen Type I; D016326:Extracellular Matrix Proteins; D017127:Glycation End Products, Advanced