ADAR1 is significantly downregulated in IPF fibroblasts; the overexpression of ADAR1 and ADAR2 reestablishes the expression levels of miRNA-21, PELI1, and SPRY2 in fibroblasts of patients with IPF.
ADAR1 is significantly downregulated in IPF fibroblasts; the overexpression of ADAR1 and ADAR2 reestablishes the expression levels of miRNA-21, PELI1, and SPRY2 in fibroblasts of patients with IPF.
Patients with AE-IPF showed higher levels of serum adiponectin and leptin than those at initial diagnosis of IPF (p = 0.007 and p = 0.027, respectively).
These studies support a potential role for HIF1A or ADORA2B antagonists in the treatment of IPF.-Philip, K., Mills, T. W., Davies, J., Chen, N.-Y., Karmouty-Quintana, H., Luo, F., Molina, J. G., Amione-Guerra, J., Sinha, N., Guha, A., Eltzschig, H. K., Blackburn, M. R. HIF1A up-regulates the ADORA2B receptor on alternatively activated macrophages and contributes to pulmonary fibrosis.
Previous reports suggested the contributory effect of receptor for advanced glycation end products (RAGE) to the pathogenesis of IPF.But the findings are controversial.
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.
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.
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.
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.
In patients with idiopathic pulmonary fibrosis (IPF), decreased blood levels of RAGE, a biomarker of AEC1 health, were associated with more rapid disease progression.
Importantly, in a mouse model of idiopathic pulmonary fibrosis (RAGE-/-), reconstitution of RAGE efficiently restored DSB-repair and reversed pathological anomalies.
TLR4 is linked with innate immunity that programs local airway inflammation, and RAGE participates in mediating fibroproliferative remodeling in idiopathic pulmonary fibrosis.
To determine whether these same cell types also synthesize ANG peptides de novo within the fibrotic human lung in situ, we subjected paraffin sections of normal and fibrotic (idiopathic pulmonary fibrosis, IPF) human lung to immunohistochemistry (IHC) and in situ hybridization to detect ANG peptides and angiotensinogen (AGT) mRNA.