Relative Roles of TGF-β and IGFBP-5 in Idiopathic Pulmonary Fibrosis

Abstract EN

Although most evident in the skin, the process of scarring, or fibrosis, occurs in all major organs because of impaired epithelial self-renewal.

No current therapy exists for Idiopathic pulmonary fibrosis.

The major profibrotic factor is TGF-β1 and developing inhibitors is an area of active research.

Recently, IGFBP-5 has also been identified as a profibrotic factor, and studies suggest that, while both TGF-β1 and IGFBP-5 activate mesenchymal cells to increase collagen and fibronectin production, their effects on epithelial cells are distinct.

TGF-β1 induces cell death and/or EMT in the epithelial cells, exacerbating the disruption of tissue architecture.

In contrast, IGFBP-5 induces epithelial cell spreading over collagen or fibronectin matrices, increases secretion of laminin, the epithelial basement membrane, and enhances the survival of epithelial cells in nutrient-poor conditions, as exists in scar tissue.

Thus, IGFBP-5 may enhance repair and may be an important target for antifibrotic therapies.