Figure 1.

RAGE expression in human IPF and in experimental mouse models of pulmonary fibrosis.

(a) In human lungs, overall expression of membrane receptor for advanced glycation endproducts RAGE (mRAGE) and soluble RAGE (sRAGE) is decreased in IPF compared with healthy lungs. In the lungs, RAGE expression is most abundant in the lung epithelium, most notably in the type 1 alveolar epithelial cells, which are diminished in IPF. However, it is suggested that RAGE expression may still be expressed in other cell types, specifically in fibrotic foci (FF). Systemically, sRAGE levels are reduced in subjects with IPF compared with healthy subjects. (b) In experimental models of IPF in mice, exposure to bleomycin, asbestos, or silica causes a decrease in whole-lung levels of both mRAGE and sRAGE. In the bleomycin model, RAGE-knockout (RAGE−/−) mice are protected from bleomycin-induced fibrosis as compared with wild-type (WT) mice. In the asbestos model, RAGE−/− mice had exacerbated fibrosis in response to asbestos exposure compared with WT mice. In the crystalline silica model, WT and RAGE−/− mice exhibited a similar magnitude of fibrosis, but RAGE−/− mice showed a more diffuse pattern of fibrosis as compared with the classical nodular fibrosis seen in WT mice. Extensive aging of mice results in the spontaneous development of features of fibrosis in RAGE−/− mice as compared with aged WT mice. The effects of aging on overall RAGE expression in WT mice remains to be investigated.

IPF, idiopathic pulmonary fibrosis.