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Role of vitronectin and fibronectin receptors in oral mucosal and dermal myofibroblast differentiation

Lygoe, K. A., Wall, I., Stephens, Philip and Lewis, M. P. 2007. Role of vitronectin and fibronectin receptors in oral mucosal and dermal myofibroblast differentiation. Biology of the Cell 99 (11) , pp. 601-614. 10.1042/BC20070008

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Abstract

Background information. 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-β1 (transforming growth factor-β1)-induced myofibroblastic differentiation [upregulation of the expression of -sma (-smooth muscle actin)], although analysis of unstimulated cells indicated that HOFs contained higher basal levels of -sma than HDFs (P<0.05). Functional blocking antibodies against the integrin subunits 5 (fibronectin) or v (vitronectin) were used to determine whether the effects of TGF-β1 were regulated via integrin signalling pathways. -sma expression in both HOFs and HDFs was down-regulated by antibodies against both 5 and v. Functionally, TGF-β1 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-β1 (P<0.05). When TGF-β1-stimulated cells were incubated with blocking antibodies against 5 and v, gel contraction was decreased to that of non-stimulated cells; however, blocking v or 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-β1-induced myofibroblastic differentiation are common to both HOFs and HDFs, and appear to require differential integrin usage; up-regulation of -sma expression and increases in collagen gel contraction are vitronectin- and fibronectin-receptor-dependent processes, whereas wound re-population is not.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Dentistry
Subjects: R Medicine > RK Dentistry
Uncontrolled Keywords: differentiation; integrin receptor; myofibroblast; oral healing; transforming growth factor-β1 (TGF-β1)
Publisher: Wiley-Blackwell
ISSN: 0248-4900
Last Modified: 04 Jun 2017 03:08
URI: http://orca.cf.ac.uk/id/eprint/17262

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