Ursolic acid alleviates airway-vessel remodeling and muscle consumption in cigarette smoke-induced emphysema rats.
BMC Pulm Med. 2019 Jun 6 ;19(1):103. Epub 2019 Jun 6. PMID: 31170951
BACKGROUND: This study assessed the effects of ursolic acid (UA) on airway-vessel remodeling and muscle atrophy in cigarette smoke (CS)-induced emphysema rats and investigated potential underlying mechanisms.
METHODS: Emphysema was induced in a rat model with 3 months of CS exposure. Histology and immunohistochemistry (IHC) stains were used to assess airway-vessel remodeling and muscle atrophy-associated changes. Levels of cleaved-caspase3, 8-OHdG, and S100A4 were measured in airways and associated vessels to evaluate cell apoptosis, oxidant stress, epithelial-to-mesenchymal transition (EMT), and endothelial-to-mesenchymal transition (EndMT)-associated factors. Western blot and/or IHC analyses were performed to measure transforming growth factor-beta 1(TGF-β1)/Smad2.3, alpha-smooth muscle actin (α-SMA), and insulin-like growth factor 1 (IGF1) expression. We also gave cultured HBE and HUVEC cells Cigarette Smoke Extract (CSE) administration and UA intervention. Using Western blot method to measure TGF-β1/Smad2.3, α-SMA, S100A4, and IGF1 molecules expression.
RESULTS: UA decreased oxidant stress and cell apoptosis in airway and accompanying vascular walls of cigarette smoke-induced emphysema model rats. UA alleviated EMT, EndMT, changes associated with airway-vessel remodeling and muscle atrophy. The UA effects were associated with IGF1 and TGF-β1/Smad2.3 pathways.
CONCLUSIONS: UA reduced EMT, EndMT, airway-vessel remodeling, and musculi soleus atrophy in CS-induced emphysema model rats at least partly through IGF1 and TGF-β1/Smad2.3 signaling pathways.