Epithelial injury induces an innate repair mechanism linked to cellular senescence and fibrosis involving igf-binding protein-5

G.J. Allan, J. Beattie, D.J. Flint

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Fibrosis is associated with epithelial repair. It involves the activation of fibroblasts, increased production of extracellular matrix proteins and transdifferentiation to contractile, myofibroblasts that 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 that can manifest as, for example, idiopathic pulmonary fibrosis, 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 (TGFB1), 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, IGF-binding protein-5 (IGFBP5). IGFBP5 has also been shown to induce similar effects to TGFB1, 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 IGFBP5 and identify some of the therapeutic targets which might be used to ameliorate these diseases of unknown cause.
Original languageEnglish
Pages (from-to)155-164
Number of pages10
JournalJournal of Endocrinology
Volume199
Issue number2
DOIs
Publication statusPublished - Nov 2008

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Cell Aging
Insulin-Like Growth Factor Binding Protein 5
Carrier Proteins
Fibrosis
Wounds and Injuries
Epithelial-Mesenchymal Transition
Fibroblasts
Idiopathic Pulmonary Fibrosis
Myofibroblasts
Extracellular Matrix Proteins
Platelet Activation
Transforming Growth Factors
Wound Healing
Cell Movement
Intercellular Signaling Peptides and Proteins
Anti-Inflammatory Agents
Epithelium
Epithelial Cells
Skin

Keywords

  • epithelial injury
  • innate repair mechanism
  • cellular senescence
  • fibrosis
  • growth factor axis

Cite this

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abstract = "Fibrosis is associated with epithelial repair. It involves the activation of fibroblasts, increased production of extracellular matrix proteins and transdifferentiation to contractile, myofibroblasts that 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 that can manifest as, for example, idiopathic pulmonary fibrosis, 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 (TGFB1), 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, IGF-binding protein-5 (IGFBP5). IGFBP5 has also been shown to induce similar effects to TGFB1, 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 IGFBP5 and identify some of the therapeutic targets which might be used to ameliorate these diseases of unknown cause.",
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Epithelial injury induces an innate repair mechanism linked to cellular senescence and fibrosis involving igf-binding protein-5. / Allan, G.J.; Beattie, J.; Flint, D.J.

In: Journal of Endocrinology, Vol. 199, No. 2, 11.2008, p. 155-164.

Research output: Contribution to journalArticle

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