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


BİRBEN E., ŞAHİNER Ü. M., Kalayci C. Ö.

Turkish Journal of Medical Sciences, cilt.53, sa.1, ss.160-170, 2023 (SCI-Expanded) identifier identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 53 Sayı: 1
  • Basım Tarihi: 2023
  • Doi Numarası: 10.55730/1300-0144.5569
  • Dergi Adı: Turkish Journal of Medical Sciences
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, CAB Abstracts, EMBASE, MEDLINE, Veterinary Science Database, TR DİZİN (ULAKBİM)
  • Sayfa Sayıları: ss.160-170
  • Anahtar Kelimeler: Asthma, airway cells, angiogenesis, RAGE, remodeling
  • Hacettepe Üniversitesi Adresli: Evet

Özet

Background/aim: 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. Materials and 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. Conclusion: Activation of RAGE pathway may contribute to asthma pathogenesis by increasing the expression of several asthma-related genes. These findings suggest that suppression of RAGE signaling may be an alternative candidate for treating asthma.