Ying Xie1, Ye Wang, Chuanyue Zong, Jiawen Cheng. 1. Department of Anesthesiology, Huai'an Hospital Affiliated with Xuzhou Medical College and Huai'an Second People's Hospital, Huaian, China.
Abstract
BACKGROUND: Heme oxygenase-1 (HO-1) contributes to the pathogenesis of pulmonary fibrosis. However, the expression of HO-1 in fibroblasts under fibrotic conditions has not been studied. METHODS: This study was conducted to investigate the expression of HO-1 in lung fibroblasts from mice and humans under fibrotic conditions by Western blot. RESULTS: We found that the expression of HO-1 was significantly decreased in lung fibroblasts isolated from bleomycin-challenged mice in comparison with control mice. Transforming growth factor-β (TGF-β) inhibited HO-1 expression and induced differentiation in human lung fibroblasts. Pretreatment with nuclear factor-κB (NF-κB) activation inhibitor or knockdown of the NF-κB p65 subunit attenuated TGF-β-induced inhibition of HO-1 expression and differentiation in human lung fibroblasts. Similarly, lysophosphatidic acid (LPA) induced TGF-β expression and decreased HO-1 expression in human lung fibroblasts. Interestingly, pretreatment with neutralized anti-TGF-β antibody attenuated LPA effects in human lung fibroblasts. CONCLUSION: These data suggested that TGF-β inhibited HO-1 expression in human lung fibroblasts through activation of NF-κB.
BACKGROUND:Heme oxygenase-1 (HO-1) contributes to the pathogenesis of pulmonary fibrosis. However, the expression of HO-1 in fibroblasts under fibrotic conditions has not been studied. METHODS: This study was conducted to investigate the expression of HO-1 in lung fibroblasts from mice and humans under fibrotic conditions by Western blot. RESULTS: We found that the expression of HO-1 was significantly decreased in lung fibroblasts isolated from bleomycin-challenged mice in comparison with control mice. Transforming growth factor-β (TGF-β) inhibited HO-1 expression and induced differentiation in human lung fibroblasts. Pretreatment with nuclear factor-κB (NF-κB) activation inhibitor or knockdown of the NF-κB p65 subunit attenuated TGF-β-induced inhibition of HO-1 expression and differentiation in human lung fibroblasts. Similarly, lysophosphatidic acid (LPA) induced TGF-β expression and decreased HO-1 expression in human lung fibroblasts. Interestingly, pretreatment with neutralized anti-TGF-β antibody attenuated LPA effects in human lung fibroblasts. CONCLUSION: These data suggested that TGF-β inhibited HO-1 expression in human lung fibroblasts through activation of NF-κB.