IGFBP-5 induces epithelial and fibroblast responses consistent with the fibrotic response.
Fibrosis involves activation of fibroblasts, increased production of collagen and fibronectin and transdifferentiation into contractile myofibroblasts. The process resembles aspects of wound-healing but remains unresolved and can be life-threatening when manifest in the kidneys, lungs and liver, in particular. The causes are largely unknown, but recent suggestions that repetitive micro-injury results in the eventual failure of epithelial cell repair due to replicative senescence are gaining favour. This is consistent with the onset of fibrotic diseases in middle age. Because epithelial injury often involves blood loss, inflammatory responses associated with the fibrotic response have been considered as therapeutic targets. However, this has proved largely unsuccessful and focus is now switching to earlier events in the process. These include EMT (epithelial-mesenchymal transition) and fibroblast activation in the absence of inflammation. TGFbeta1 (transforming growth factor-beta1) induces both EMT and fibroblast activation and is considered to be a major pro-fibrotic factor. Recently, IGFBP-5 [IGF (insulin-like growth factor)-binding protein-5] has also been shown to induce similar effects on TGFbeta1, and is strongly implicated in the process of senescence. It also stimulates migration of peripheral blood mononuclear cells, implicating it in the inflammatory response. In this paper, we examine the evidence for a role of IGFBP-5 in fibrosis and highlight its structural relationship with other matrix proteins and growth factors also implicated in tissue remodelling.
Sureshbabu
Angara
A
SIPBS, Strathclyde University, Glasgow G4 0NR, UK.
Okajima
Hiroshi
H
Yamanaka
Daisuke
D
Shastri
Surya
S
Tonner
Elizabeth
E
Rae
Colin
C
Szymanowska
Malgorzata
M
Shand
John H
JH
Takahashi
Shin-Ichiro
S
Beattie
James
J
Allan
Gordon J
GJ
Flint
David J
DJ
D000818:Animals; D004848:Epithelium / Q000378:metabolism* / Q000473:pathology; D005347:Fibroblasts / Q000378:metabolism*; D005355:Fibrosis / Q000378:metabolism / Q000473:pathology; D006801:Humans; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000378:metabolism / Q000502:physiology*; D008648:Mesoderm / Q000378:metabolism / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
D018975:Insulin-Like Growth Factor Binding Protein 5; D053773:Transforming Growth Factor beta1