Effects Of Hypoxia On Airway Remodeling-Associated Factors In Human Bronchial Epithelial Cells

Objective:To explore the effects of hypoxia on the expressions of airway remodeling-associated factors,such as matrix metalloproteinase-9?MMP-9?and transforming growth factor?₁?TGF-?₁?in human bronchial epithelial?16HBE?cells,and to clarify the possible signaling pathway.Methods:16HBE cells were cultured under normoxia or hypoxia?2%O₂?for 6?12?24 hours.A certain time treated group with highest level of MMP-9 and TGF-?₁ were pretreated with epidermal growth factor receptor?EGFR?inhibitor AG1478 and hypoxia-inducible factor-1??HIF-1??inhibitor Lificiguat?YC-1?.A certain time treated group with highest level of HIF-1?were pretreated with epidermal growth factor receptor?EGFR?inhibitor AG1478.Cell survival rate was measured by CCK-8 method.The mRNA levels of MMP-9 and TGF-?₁ were detected by Quantitative Real-time PCR.The protein levels of HIF-1?,MMP-9 and TGF-?₁ were measured by Western blot.Results:In hypoxia group,the levels of MMP-9,TGF-?₁ mRNA and MMP-9,TGF-?₁ protein expressions were significantly increased compared with those in control group?all P<0.05?.Pretreatment with EGFR inhibitor AG1478?HIF-1?inhibitor YC-1 could inhibit the level of MMP-9,TGF-?₁ mRNA and MMP-9,TGF-?₁ protein expressions induced by hypoxia?P<0.05?.AG1478 suppressed the high expression of HIF-1?induced by hypoxia?P<0.05?.Conclusion:Hypoxia can up-regulate the expressions of airway remodeling-associated factors,such as MMP-9 and TGF-?₁ via EGFR's induction of HIF-1?signaling pathway.