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

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

研究成果: Article査読

33 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)179-188
ページ数10
ジャーナルAmerican Journal of Respiratory Cell and Molecular Biology
41
2
DOI
出版ステータスPublished - 01-08-2009
外部発表はい

All Science Journal Classification (ASJC) codes

  • 分子生物学
  • 呼吸器内科
  • 臨床生化学
  • 細胞生物学

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