The research discovered a novel role for the receptor for advanced glycation end-products (RAGE) in which it acts as a master regulator for DNA double-strand break repair.In doing so, Kumar et al. may have made a breakthrough that could redefine the translational approaches of IPF.
In patients with idiopathic pulmonary fibrosis (IPF), decreased blood levels of RAGE, a biomarker of AEC1 health, were associated with more rapid disease progression.
To examine (1) the association between IPF risk and variation at rs2070600, a functional missense variant in AGER (the gene that codes for RAGE), and (2) the associations between plasma-soluble RAGE (sRAGE) levels with disease severity and time to death or lung transplant in IPF.
Importantly, in a mouse model of idiopathic pulmonary fibrosis (RAGE-/-), reconstitution of RAGE efficiently restored DSB-repair and reversed pathological anomalies.
Previous reports suggested the contributory effect of receptor for advanced glycation end products (RAGE) to the pathogenesis of IPF.But the findings are controversial.
TLR4 is linked with innate immunity that programs local airway inflammation, and RAGE participates in mediating fibroproliferative remodeling in idiopathic pulmonary fibrosis.
Significant down-regulation of RAGE was observed in lung homogenate and alveolar epithelial type II cells from patients with idiopathic pulmonary fibrosis, as well as in bleomycin-treated mice, demonstrated by RT-PCR, Western blotting, and immunohistochemistry.
Combined with data from other studies on mouse models of pulmonary fibrosis and human IPF tissues indicate that loss of RAGE contributes to IPF pathogenesis.