Arg-Gly-Asp-containing peptides expose novel collagen receptors on fibroblasts: implications for wound healing.
Integrins are a family of cell-surface receptors intimately involved in the interactions of cells with their extracellular matrix. These receptors comprise an alpha and beta subunit in noncovalent association and many have been shown to recognize and bind an arginine-glycine-aspartate (RGD) sequence contained within their specific extracellular matrix ligand. Fibroblasts express integrin receptors belonging to two major subfamilies. Some of the members within the subfamily defined by beta 1 (VLA) are receptors for collagen but, perhaps surprisingly, the other major subfamily of integrins on fibroblasts--that defined by the alpha chain of the vitronectin receptor, alpha v--all appear to bind primarily vitronectin and/or fibronectin. In the present study we show that RGD-containing peptides expose cryptic binding sites on the alpha v-associated integrins enabling them to function as collagen receptors. The addition of RGD-containing peptides to fibroblasts cultured on type I collagen induced dramatic cell elongation and, when the cells were contained within collagen matrices, the peptides induced marked contraction of the gels. These processes were inhibited by Fab fragments of a monoclonal antibody against an alpha v integrin. Also, alpha v-associated integrins from cell lysates bound to collagen I affinity columns in the presence, but not in the absence, of RGD-containing peptides. These data suggest a novel regulatory control for integrin function. In addition, because the cryptic collagen receptors were shown to be implicated in the contraction of collagen gels, the generation of such binding forces suggests that this may be the major biological role for these integrins in processes such as wound healing.
Agrez
M V
MV
Discipline of Surgical Science, Faculty of Medicine, University of Newcastle, Royal Newcastle Hospital, New South Wales, Australia.
Bates
R C
RC
Boyd
A W
AW
Burns
G F
GF
D000595:Amino Acid Sequence; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000378:metabolism; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000187:drug effects* / Q000378:metabolism; D038981:Receptors, Collagen; D014945:Wound Healing / Q000502:physiology*
D016023:Integrins; D010455:Peptides; D011956:Receptors, Cell Surface; D038981:Receptors, Collagen; D003094:Collagen