Induction of beta 1 integrin synthesis by recombinant platelet-derived growth factor (PDGF-AB) correlates with an enhanced migratory response of human dermal fibroblasts to various extracellular matrix proteins.
Cell migration plays a major role during wound healing and is tightly controlled by a variety of growth factors and extracellular matrix proteins. The experiments reported here have been designed to study whether defined beta 1 integrins are involved in the platelet-derived growth-factor-AB (PDGF-AB)-modulated migratory response to collagen type I and to fibronectin. Preincubation of fibroblasts with PDGF-AB resulted in an up to 2.5-fold increase in the migratory response to collagen type I as well as fibronectin and to enhanced synthesis and cell surface expression of the alpha 2, alpha 3, alpha 5, and beta 1 integrin subunits. Function-blocking monoclonal antibodies against the common beta 1 integrin subunit dose-dependently inhibited the PDGF-AB-augmented migration of fibroblasts to collagen type I and fibronectin. The PDGF-AB-induced migration to collagen type I was also inhibited by antibodies against the alpha 2 integrin subunit, whereas the corresponding migration to fibronectin was almost completely blocked by the combined application of antibodies against the alpha 3 and the alpha 5 integrin subunits. Taken together, up-regulation of integrin synthesis and expression by human recombinant PDGF-AB correlate with an increase in the migratory response of dermal human fibroblasts to various extracellular matrix proteins and thus may contribute to an efficient regulation of cell migration during wound healing and tissue repair.
Kirchberg
K
K
Department of Dermatology, University of Düsseldorf, Germany.
Lange
T S
TS
Klein
E C
EC
Jungtäubl
H
H
Heinen
G
G
Meyer-Ingold
W
W
Scharffetter-Kochanek
K
K
D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D003094:Collagen / Q000494:pharmacology; D016326:Extracellular Matrix Proteins / Q000494:pharmacology*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D005353:Fibronectins / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D019012:Integrin beta1; D016023:Integrins / Q000096:biosynthesis*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011233:Precipitin Tests; D011994:Recombinant Proteins / Q000494:pharmacology; D012867:Skin / Q000166:cytology / Q000187:drug effects; D012879:Skin Physiological Phenomena
D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D019012:Integrin beta1; D016023:Integrins; D010982:Platelet-Derived Growth Factor; D011994:Recombinant Proteins; C095477:platelet-derived growth factor AB; D003094:Collagen