Exp Mol Med.  2007 Oct;39(5):663-672.

Recombinant tetra-cell adhesion motifs supports adhesion, migration and proliferation of keratinocytes/fibroblasts, and promotes wound healing

• Jung MY
• Thapa N
• Kim JE
• Yang JD
• Cho BC
• Kim IS

Abstract

An extracellular matrix protein plays an important role in skin wound healing. In the present study, we engineered a recombinant protein encompassing the 9th and 10th type III domains of fibronectin, and 4th FAS1 domain of beta ig-h3. This recombinant protein, in total, harbors four known-cell adhesion motifs for integrins: Pro-His-Ser-Arg-Asn (PHSRN) and Arg-Gly-Asp (RGD) in 9th and 10th type III domains of fibronectin, respectively, and Glu-Pro-Asp-Ile-Met (EPDIM) and Try-His (YH) in 4th FAS1 domain of big-h3, were designated to tetra-cell adhesion motifs (T-CAM). In vitro studies showed T-CAM supporting adhesion, migration and proliferation of different cell types including keratinocytes and fibroblasts. In an animal model of full-thickness skin wound, T-CAM exhibited excellent wound healing effects, superior to both 4th FAS1 domain of beta ig-h3 or 9th and 10th type III domains of fibronectin. Based on these results, T-CAM can be applied where enhancement of cell adhesion, migration and proliferation are desired, and it could be developed into novel wound healing drug.

Keyword

betaIG-H3 protein; cell adhesion; cell movement; cell proliferation; fibronectin; wound healing

MeSH Terms

Amino Acid Motifs
Animals
Cell Adhesion/*drug effects
Cell Line
Cell Movement/*drug effects
Cell Proliferation/*drug effects
Extracellular Matrix Proteins/chemistry/genetics/pharmacology
Fibroblasts/cytology/drug effects/physiology
Fibronectins/chemistry/genetics/*pharmacology
Humans
Keratinocytes/cytology/drug effects/physiology
Mice
NIH 3T3 Cells
Rabbits
Recombinant Fusion Proteins/chemistry/genetics/pharmacology
Transforming Growth Factor beta/chemistry/genetics/pharmacology
Wound Healing/*drug effects/physiology