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Open Access Research

Platelet-derived growth factor alpha and beta receptors have overlapping functional activities towards fibroblasts

Johanna Donovan1*, Xu Shiwen1, Jill Norman2 and David Abraham1

Author Affiliations

1 Centre for Rheumatology and Connective Tissue Diseases and Division of Medicine, UCL Medical School, Royal Free Campus, London, UK

2 Centre for Nephrology, Division of Medicine, UCL Medical School, Royal Free Campus, London, UK

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Fibrogenesis & Tissue Repair 2013, 6:10  doi:10.1186/1755-1536-6-10

Published: 10 May 2013

Abstract

Background

Platelet-derived growth factor (PDGF) signalling is essential for many key cellular processes in mesenchymal cells. As there is redundancy in signalling between the five PDGF ligand isoforms and three PDGF receptor isoforms, and deletion of either of the receptors in vivo produces an embryonic lethal phenotype, it is not know which ligand and receptor combinations mediate specific cellular functions. Fibroblasts are key mediators in wound healing and tissues repair. Recent clinical trials using broad spectrum tyrosine kinase inhibitors in fibrotic diseases have highlighted the need to further examine the specific cellular roles each of the tyrosine kinases plays in fibrotic processes. In this study, we used PDGFR-specific neutralising antibodies to dissect out receptor-specific signalling events in fibroblasts in vitro, to further understand key cellular processes involved in wound healing and tissue repair.

Results

Neutralising antibodies against PDGFRs were shown to block signalling through PDGFRα and PDGFRβ receptors, reduce human PDGF-AA and PDGF-BB-induced collagen gel remodelling in dermal fibroblasts, and reduce migration stimulated by all PDGF ligands in human dermal and lung fibroblasts.

Conclusions

PDGFRα and PDGFRβ neutralising antibodies can be a useful tool in studying PDGFR isoform-specific cellular events.