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

Figure 1

Differential effects of TGF-β1 and IGFBP-5 on mesenchymal and epithelial cells. In fibroblasts, TGF-β1 activates the Smad pathway resulting in activation of genes associated with fibrosis such as collagen, fibronectin, and CTGF. CTGF in turn further activates this process via an aVb3 integrin-dependent mechanism. IGFBP-5 binds to and activates α2β1 integrins and is capable of activating MAPK pathways in similar fashion to CTGF. In contrast, TGF-β1 activation of the Smad pathway results in an apoptotic pathway in epithelial cells, whereas IGFBP-5, again acting through α2β1 integrin, stimulates an adhesive, prosurvival pathway. Thus, IGFBP-5 enhances TGF-β1 actions in the mesenchymal compartment but inhibits them in the epithelium.