Recombinant tetra-cell adhesion motifs supports adhesion, migration and proliferation of keratinocytes/fibroblasts, and promotes wound healing.
An extracellular matrix protein plays an important role in skin wound healing. In the present study, we engineered a recombinant protein encompassing the 9(th) and 10(th) type III domains of fibronectin, and 4(th) FAS1 domain of betaig-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 9(th) and 10(th) type III domains of fibronectin, respectively, and Glu-Pro-Asp-Ile-Met (EPDIM) and Try-His (YH) in 4(th) FAS1 domain of betaig-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 4(th) FAS1 domain of betaig-h3 or 9(th) and 10(th) 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.
Jung
Mi Yeon
MY
Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu 700-422, Korea.
Thapa
Narendra
N
Kim
Jung Eun
JE
Yang
Jung Duk
JD
Cho
Byung Chae
BC
Kim
In San
IS
D020816:Amino Acid Motifs; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects*; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D016326:Extracellular Matrix Proteins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D005353:Fibronectins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D051379:Mice; D041681:NIH 3T3 Cells; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology; D000099222:betaIG-H3 Protein
D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D011993:Recombinant Fusion Proteins; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein