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This Article Accepted manuscript (PDF) All Versions of this Article: JOE-08-0269v1 199/2/155    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Flint, D. Articles by Beattie, J. Search for Related Content PubMed PubMed Citation Articles by Flint, D. Articles by Beattie, J.

D Flint, Glasgow, G1 1XW, United Kingdom
G Allan, The University of Strathclyde, Glasgow, United Kingdom
J Beattie, Glasgow, United Kingdom

Correspondence: David Flint, Email: David.Flint{at}strath.ac.uk

Abstract

Fibrosis is associated with epithelial repair. It involves activation of fibroblasts, increased production of extracellular matrix proteins, and transdifferentiation to contractile, myofibroblasts which aid in wound contraction. This provisional matrix plugs the injured epithelium and provides a scaffold for epithelial cell migration, involving an epithelial-mesenchymal transition (EMT). When epithelial injury involves blood loss, this leads to platelet activation, the production of several growth factors, and an acute inflammatory response. Under normal circumstances the epithelial barrier is repaired and the inflammatory response resolves. However, in fibrotic disease, the fibroblast response continues, resulting in unresolved wound-healing. The fibrotic diseases range from scleroderma, where the problem may be restricted to the skin and where it is not life-threatening, through to systemic forms which can manifest as, for example, idiopathic pulmonary fibrosis (IPF), in which death is inevitable within 3-5 years. Anti-inflammatory treatments have failed to ameliorate the disease condition and focus has instead turned to transforming growth factor-β1 (TGFβ1), since it induces many of the processes involved, including fibroblast activation and EMT. Most recently however, a new player in this process has been described, insulin-like growth factor binding protein-5 (IGFBP-5). IGFBP-5 has also been shown to induce similar effects to TGF-β1, but, in addition, it is strongly implicated in the process of senescence which is now believed to be a significant factor in these diseases. We examine the evidence for this role of IGFBP-5 and identify some of the therapeutic targets which might be used to ameliorate these diseases of unknown cause.