Insulin-like growth factor-binding protein-5 induces pulmonary fibrosis and triggers mononuclear cellular infiltration

Hidekata Yasuoka, Zhihong Zhou, Joseph M. Pilewski, Tim D. Oury, Augustine M K Choi, Carol A. Feghali-Bostwick

Research output: Contribution to journalArticle

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Abstract

We have recently shown that insulin-like growth factor-binding protein (IGFBP)-5 is overexpressed in idiopathic pulmonary fibrosis lung tissues and increases collagen and fibronectin deposition. Here, we further examined the effect of IGFBP-5 in vivo by intratracheal administration of replication-deficient adenovirus expressing human IGFBP-5 (Ad5), IGFBP-3 (Ad3), or no cDNA (cAd) to wild-type mice. Increased cellular infiltration and extracellular matrix deposition were observed in mice after Ad5 administration compared with Ad3 and cAd. Mononuclear cell infiltration consisted predominantly of T lymphocytes at day 8. By day 14, the number of infiltrating T cells decreased, whereas that of B cells and monocytes/macrophages increased. IGFBP-5 also induced migration of peripheral blood mononuclear cells in vitro, suggesting that in vivo mononuclear cell infiltration may be the direct result of IGFBP-5 expression. α-Smooth muscle actin and Mucin-1 co-localized in cells of mice treated with Ad5, suggesting that IGFBP-5 induced epithelial-mesenchymal transition. In addition, exogenous IGFBP-5 induced α-smooth muscle actin expression in primary fibroblasts and epithelial-mesenchymal transition of pulmonary epithelial cells in vitro. In conclusion, our results suggest that overexpression of IGFBP-5 in mouse lung results in fibroblast activation, increased extracellular matrix deposition, and myofibroblastic changes. Thus, the IGFBP-5-induced fibrotic phenotype in vivo may represent a novel model to better understand the pathogenesis of fibrosis.

Original languageEnglish
Pages (from-to)1633-1642
Number of pages10
JournalAmerican Journal of Pathology
Volume169
Issue number5
DOIs
Publication statusPublished - 2006 Nov
Externally publishedYes

Fingerprint

Insulin-Like Growth Factor Binding Protein 5
Pulmonary Fibrosis
Insulin-Like Growth Factor Binding Protein 3
Epithelial-Mesenchymal Transition
Lung
Extracellular Matrix
Smooth Muscle
Actins
Fibroblasts
T-Lymphocytes
Human Adenoviruses
Mucin-1
Idiopathic Pulmonary Fibrosis
Fibronectins
Monocytes
Blood Cells
Fibrosis
B-Lymphocytes
Collagen
Complementary DNA

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Yasuoka, H., Zhou, Z., Pilewski, J. M., Oury, T. D., Choi, A. M. K., & Feghali-Bostwick, C. A. (2006). Insulin-like growth factor-binding protein-5 induces pulmonary fibrosis and triggers mononuclear cellular infiltration. American Journal of Pathology, 169(5), 1633-1642. https://doi.org/10.2353/ajpath.2006.060501

Insulin-like growth factor-binding protein-5 induces pulmonary fibrosis and triggers mononuclear cellular infiltration. / Yasuoka, Hidekata; Zhou, Zhihong; Pilewski, Joseph M.; Oury, Tim D.; Choi, Augustine M K; Feghali-Bostwick, Carol A.

In: American Journal of Pathology, Vol. 169, No. 5, 11.2006, p. 1633-1642.

Research output: Contribution to journalArticle

Yasuoka, Hidekata ; Zhou, Zhihong ; Pilewski, Joseph M. ; Oury, Tim D. ; Choi, Augustine M K ; Feghali-Bostwick, Carol A. / Insulin-like growth factor-binding protein-5 induces pulmonary fibrosis and triggers mononuclear cellular infiltration. In: American Journal of Pathology. 2006 ; Vol. 169, No. 5. pp. 1633-1642.
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