Determination of the effects of advanced glycation end products receptor polymorphisms and its activation on structural cell responses and inflammation in asthma

Turk J Med Sci. 2023 Feb;53(1):160-170. doi: 10.55730/1300-0144.5569. Epub 2023 Feb 22.

Abstract

Background: Advanced glycation end products receptor (RAGE) is a pattern recognition receptor which attracted attention in chronic airway diseases recently. This study aimed to determine the association of RAGE with asthma and the cellular responses resulting from RAGE signaling pathway activation.

Methods: Asthmatic (n = 362) and healthy (n = 134) children were genotyped by PCR-RFLP. Plasma sRAGE levels were determined by ELISA. Lung structural cells were stimulated with AGEs (advanced glycation end products) and control BSA. Expressions of cytokines and protein levels were determined by real-time PCR and ELISA.

Results: : Gly82Ser and -374 T/A polymorphisms in RAGE gene were associated with lower plasma sRAGE levels (p < 0.001 and p < 0.025, respectively). AGE stimulation increased the expression of RAGE (p = 0.002), ICAM-1 (p = 0.010) and VCAM-1 (p = 0.002) in endothelial cells; TIMP-1 (p = 0.003) and MCP-1 (p = 0.005) in fibroblasts. AGE stimulation increased protein levels of IL-6 (p < 0.001) in endothelial cells; VEGF (p = 0.025) and IL-8 (p < 0.001) in fibroblasts; IL-1b (p < 0.001) and VEGF (p = 0.007) in epithelial cells.

Discussion: Activation of RAGE pathway may contribute to asthma pathogenesis by increasing the expression of several asthmarelated genes. These findings suggest that suppression of RAGE signaling may be an alternative candidate for treating asthma.

Keywords: Asthma; RAGE; airway cells; angiogenesis; remodeling.

MeSH terms

  • Asthma* / genetics
  • Child
  • Endothelial Cells* / metabolism
  • Glycation End Products, Advanced / metabolism
  • Humans
  • Inflammation
  • Receptor for Advanced Glycation End Products / genetics
  • Vascular Endothelial Growth Factor A / genetics

Substances

  • Receptor for Advanced Glycation End Products
  • Vascular Endothelial Growth Factor A
  • Glycation End Products, Advanced

Grants and funding

This study is supported by the Scientific Research Projects Coordination Unit (grant no: 013D06103001) and The Scientific and Technological Research Council of Türkiye (TÜBİTAK) with the grant no. 219S276.