The pro-fibrotic factor IGFBP-5 induces lung fibroblast and mononuclear cell migration

Hidekata Yasuoka, Yukie Yamaguchi, Carol A. Feghali-Bostwick

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

We have previously shown that insulin-like growth factor-binding protein-5 (IGFBP-5) is overexpressed in fibrotic lung tissues and that it induces production of extracellular matrix components such as collagen and fibronectin both in vitro and in vivo. We recently observed mononuclear cell infiltration in lung tissues of mice expressing IGFBP-5. We therefore examined the role of IGFBP-5 on the migration of immune cells. Migration assays demonstrated that IGFBP-5 induced migration of peripheral blood mononuclear cells (PBMCs) in a dose-dependent manner. Preferential migration of monocytes/macrophages, natural killer cells, and T cells was observed. Moreover, the CD4/CD8 ratio of migrating cells was significantly higher in vitro and in vivo in response to IGFBP-5. IGFBP-5 resulted in preferential migration of activated CD4+ T cells and monocytes. Interestingly, IGFBP-5 also induced migration of primary human lung fibroblasts. Exogenous administration of IGFBP-5 induced activation of mitogen-activated protein kinase (MAPK) signaling cascade but not PI3K in PBMCs. IGFBP-5-induced migration was blocked by the MEK1/2 inhibitor U0126, suggesting that IGFBP-5-induced migration occurs via MAPK activation. Furthermore, monocytes treated with recombinant IGFBP-5 expressed the mesenchymal markers a-smoothmuscle actin and fibronectin in vitro and in vivo, suggesting that IGFBP-5 can induce the transformation of monocytes into mesenchymal cells. Collectively, our results suggest that IGFBP-5 induces cell migration via MAPK-dependent and IGF-I-independent mechanisms.

Original languageEnglish
Pages (from-to)179-188
Number of pages10
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume41
Issue number2
DOIs
Publication statusPublished - 2009 Aug 1
Externally publishedYes

Fingerprint

Insulin-Like Growth Factor Binding Protein 5
Fibroblasts
Cell Movement
Lung
Monocytes
Mitogen-Activated Protein Kinases
T-cells
Fibronectins
Blood Cells
Blood
Chemical activation
T-Lymphocytes
Tissue
CD4-CD8 Ratio
Macrophages
Phosphatidylinositol 3-Kinases
Insulin-Like Growth Factor I
Natural Killer Cells
Infiltration
Extracellular Matrix

Keywords

  • Fibrosis
  • IGFBP-5
  • MAPK
  • Migration
  • Mononuclear cells

ASJC Scopus subject areas

  • Cell Biology
  • Pulmonary and Respiratory Medicine
  • Molecular Biology
  • Clinical Biochemistry

Cite this

The pro-fibrotic factor IGFBP-5 induces lung fibroblast and mononuclear cell migration. / Yasuoka, Hidekata; Yamaguchi, Yukie; Feghali-Bostwick, Carol A.

In: American Journal of Respiratory Cell and Molecular Biology, Vol. 41, No. 2, 01.08.2009, p. 179-188.

Research output: Contribution to journalArticle

Yasuoka, Hidekata ; Yamaguchi, Yukie ; Feghali-Bostwick, Carol A. / The pro-fibrotic factor IGFBP-5 induces lung fibroblast and mononuclear cell migration. In: American Journal of Respiratory Cell and Molecular Biology. 2009 ; Vol. 41, No. 2. pp. 179-188.
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