Role of vitronectin and fibronectin receptors in oral mucosal and dermal myofibroblast differentiation.
BACKGROUND
The activation of fibroblasts into myofibroblasts is a crucial event in healing that is linked to remodelling and scar formation, therefore we determined whether regulation of myofibroblast differentiation via integrins might affect wound healing responses in populations of patient-matched HOFs (human oral fibroblasts) compared with HDFs (human dermal fibroblasts).


RESULTS
Both the HOF and HDF cell types underwent TGF-beta1 (transforming growth factor-beta1)-induced myofibroblastic differentiation [upregulation of the expression of alpha-sma (alpha-smooth muscle actin)], although analysis of unstimulated cells indicated that HOFs contained higher basal levels of alpha-sma than HDFs (P<0.05). Functional blocking antibodies against the integrin subunits alpha 5 (fibronectin) or alpha v (vitronectin) were used to determine whether the effects of TGF-beta1 were regulated via integrin signalling pathways. alpha-sma expression in both HOFs and HDFs was down-regulated by antibodies against both alpha 5 and alpha v. Functionally, TGF-beta1 inhibited cell migration in an in vitro wound model and increased the contraction of collagen gels. Greater contraction was evident for HOFs compared with HDFs, both with and without stimulation by TGF-beta1 (P<0.05). When TGF-beta1-stimulated cells were incubated with blocking antibodies against alpha 5 and alpha v, gel contraction was decreased to that of non-stimulated cells; however, blocking alpha v or alpha 5 could not restore cellular migration in both HOFs and HDFs.


CONCLUSIONS
Despite intrinsic differences in their basal state, the cellular events associated with TGF-beta1-induced myofibroblastic differentiation are common to both HOFs and HDFs, and appear to require differential integrin usage; up-regulation of alpha-sma expression and increases in collagen gel contraction are vitronectin- and fibronectin-receptor-dependent processes, whereas wound re-population is not.
Lygoe
Kate A
KA
Division of Biomaterials and Tissue Engineering, Eastman Dental Institute, University College London, 256 Grays Inn Road, London WC1X 8LD, UK.
Wall
Ivan
I
Stephens
Philip
P
Lewis
Mark P
MP
D000199:Actins / Q000096:biosynthesis; D000906:Antibodies / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002921:Cicatrix / Q000378:metabolism; D020405:Dermis / Q000166:cytology / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D039482:Integrin alpha5 / Q000378:metabolism; D039564:Integrin alphaV / Q000378:metabolism; D009061:Mouth Mucosa / Q000166:cytology / Q000378:metabolism*; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism*; D009928:Organ Specificity / Q000502:physiology; D017469:Receptors, Fibronectin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019030:Receptors, Vitronectin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology; D019096:Vitronectin / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology
D000199:Actins; D000906:Antibodies; D005353:Fibronectins; D039482:Integrin alpha5; D039564:Integrin alphaV; D017469:Receptors, Fibronectin; D019030:Receptors, Vitronectin; D053773:Transforming Growth Factor beta1; D019096:Vitronectin