Effects of hypoxia on expressions of human airway remodeling-associated factors in airway epithelial cells / 西安交通大学学报(医学版)

ABSTRACT

Objective To explore the mechanism of hypoxia on the expressions of airway remodeling-associated factors matrix metalloproteinase-9(MMP-9)and transforming growth factor β1(TGF-β1)in human airway epithelial cells(16HBE)under hypoxia.Methods We cultured 16HBE cells under normoxia or hypoxia (20 mL/L O2)for 6,12 and 24 hours.MMP-9 and TGF-β1with higher expression were pretreated with epidermal growth factor receptor(EGFR)inhibitor AG1478 and hypoxia-inducible factor-1α(HIF-1α)inhibitor Lificiguat (YC-1).Cell survival rate was measured by CCK-8 method.The mRNA levels of MMP-9 and TGF-β1were detected by RT-PCR.The levels of HIF-1α,MMP-9 and TGF-β1protein expressions were measured by Western blot. Results In hypoxia group,the levels of MMP-9 and TGF-β1mRNA as well as protein expressions increased compared with those in the control group(all P＜ 0.05).Pretreatment with AG1478 and YC-1 could inhibit the above-mentioned changes(P＜ 0.05).AG1478 suppressed the high expression of HIF-1α induced by hypoxia. Conclusion Hypoxia can up-regulate the expressions of airway remodeling-associated factors MMP-9 and TGF-β1 via EGFR's induction of HIF-α signaling pathway.