IGFBP-5 induces epithelial and fibroblast responses consistent with the fibrotic response

Angara Sureshbabu, Hiroshi Okajima, Daisuke Yamanaka, Surya Shastri, Elizabeth Tonner, Colin Rae, M. Szymanowska, J.H. Shand, Shin-Ichiro Takahashi, J. Beattie, G.J. Allan, D.J. Flint

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

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. TGFβ1 (transforming growth factor-β1) 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 TGFβ1, 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.
LanguageEnglish
Pages882-885
Number of pages3
JournalBiochemical Society Transactions
Volume37
DOIs
Publication statusPublished - Mar 2009

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Insulin-Like Growth Factor Binding Protein 5
Fibroblasts
Epithelial-Mesenchymal Transition
Chemical activation
Transforming Growth Factors
Fibrosis
Blood
Myofibroblasts
Cell Aging
Wounds and Injuries
Fibronectins
Liver
Wound Healing
Blood Cells
Intercellular Signaling Peptides and Proteins
Repair
Collagen
Epithelial Cells
Tissue
Inflammation

Keywords

  • epithelial–mesenchymal transition
  • fibrosis
  • insulin-like growth factor
  • senescence
  • tissue injury
  • transforming growth factor-β (TGFβ)

Cite this

Sureshbabu, Angara ; Okajima, Hiroshi ; Yamanaka, Daisuke ; Shastri, Surya ; Tonner, Elizabeth ; Rae, Colin ; Szymanowska, M. ; Shand, J.H. ; Takahashi, Shin-Ichiro ; Beattie, J. ; Allan, G.J. ; Flint, D.J. / IGFBP-5 induces epithelial and fibroblast responses consistent with the fibrotic response. In: Biochemical Society Transactions. 2009 ; Vol. 37. pp. 882-885.
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Sureshbabu, A, Okajima, H, Yamanaka, D, Shastri, S, Tonner, E, Rae, C, Szymanowska, M, Shand, JH, Takahashi, S-I, Beattie, J, Allan, GJ & Flint, DJ 2009, 'IGFBP-5 induces epithelial and fibroblast responses consistent with the fibrotic response' Biochemical Society Transactions, vol. 37, pp. 882-885. https://doi.org/10.1042/BST0370882

IGFBP-5 induces epithelial and fibroblast responses consistent with the fibrotic response. / Sureshbabu, Angara; Okajima, Hiroshi; Yamanaka, Daisuke; Shastri, Surya; Tonner, Elizabeth; Rae, Colin; Szymanowska, M.; Shand, J.H.; Takahashi, Shin-Ichiro; Beattie, J.; Allan, G.J.; Flint, D.J.

In: Biochemical Society Transactions, Vol. 37, 03.2009, p. 882-885.

Research output: Contribution to journalArticle

TY - JOUR

T1 - IGFBP-5 induces epithelial and fibroblast responses consistent with the fibrotic response

AU - Sureshbabu, Angara

AU - Okajima, Hiroshi

AU - Yamanaka, Daisuke

AU - Shastri, Surya

AU - Tonner, Elizabeth

AU - Rae, Colin

AU - Szymanowska, M.

AU - Shand, J.H.

AU - Takahashi, Shin-Ichiro

AU - Beattie, J.

AU - Allan, G.J.

AU - Flint, D.J.

PY - 2009/3

Y1 - 2009/3

N2 - 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. TGFβ1 (transforming growth factor-β1) 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 TGFβ1, 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.

AB - 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. TGFβ1 (transforming growth factor-β1) 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 TGFβ1, 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.

KW - epithelial–mesenchymal transition

KW - fibrosis

KW - insulin-like growth factor

KW - senescence

KW - tissue injury

KW - transforming growth factor-β (TGFβ)

UR - http://dx.doi.org/10.1042/BST0370882

U2 - 10.1042/BST0370882

DO - 10.1042/BST0370882

M3 - Article

VL - 37

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EP - 885

JO - Biochemical Society Transactions

T2 - Biochemical Society Transactions

JF - Biochemical Society Transactions

SN - 0300-5127

ER -