Yun Gao1, Yu Chen2, Huaping Yu3, Haibing Lan2. 1. Outpatient department, Second Affiliated Hospital of Nanchang University, Nanchang 330006, China. 2. Department of Intensive Care Medicine, Second Affiliated Hospital of Nanchang University, Nanchang 330006, China. 3. Department of Respiratory Diseases, Second Affiliated Hospital of Nanchang University, Nanchang 330006, China.
Abstract
OBJECTIVE: To explore the role of macrophage migration inhibitory factor (MIF) in lung fibrosis and the possible molecular pathways involved. METHODS: Twenty male adult mice were randomized into control group and pulmonary fibrosis model group to receive intratracheal instillation of normal saline and bleomycin, respectively. Thirty days after the instillation, the level of MIF in the lung tissue of the mice was measured. Human embryonic lung fibroblasts (HLFs) were stimulated with recombinant human MIF (rMIF) and the changes in reactive oxygen species (ROS) levels, aerobic glycolysis and collagen production were measured; the effects of ROS inhibitor and glycolysis inhibitor on collagen productions were tested in rMIFstimulated HLF cells. RESULTS: Compared with the control mice, the mice with bleomycin-induced lung fibrosis exhibited significantly increased levels of MIF in the lung tissue and bronchoalveolar lavage fluid (BALF). ROS levels, aerobic glycolysis and collagen production were all increased in HLFs in response to rMIF stimulation; the enhancement of aerobic glycolysis and collagen production induced by rMIF and hydrogen peroxide were obviously suppressed by ROS inhibitor; the application of glycolysis inhibitor obviously inhibited rMIF-and hydrogen peroxide-induced increase of collagen production in HLFs. CONCLUSIONS: rMIF participates in the development of pulmonary fibrosis in mice probably by up-regulating aerobic glycolysis via ROS to promote collagen production in fibroblasts.
OBJECTIVE: To explore the role of macrophage migration inhibitory factor (MIF) in lung fibrosis and the possible molecular pathways involved. METHODS: Twenty male adult mice were randomized into control group and pulmonary fibrosis model group to receive intratracheal instillation of normal saline and bleomycin, respectively. Thirty days after the instillation, the level of MIF in the lung tissue of the mice was measured. Humanembryonic lung fibroblasts (HLFs) were stimulated with recombinant humanMIF (rMIF) and the changes in reactive oxygen species (ROS) levels, aerobic glycolysis and collagen production were measured; the effects of ROS inhibitor and glycolysis inhibitor on collagen productions were tested in rMIFstimulated HLF cells. RESULTS: Compared with the control mice, the mice with bleomycin-induced lung fibrosis exhibited significantly increased levels of MIF in the lung tissue and bronchoalveolar lavage fluid (BALF). ROS levels, aerobic glycolysis and collagen production were all increased in HLFs in response to rMIF stimulation; the enhancement of aerobic glycolysis and collagen production induced by rMIF and hydrogen peroxide were obviously suppressed by ROS inhibitor; the application of glycolysis inhibitor obviously inhibited rMIF-and hydrogen peroxide-induced increase of collagen production in HLFs. CONCLUSIONS:rMIF participates in the development of pulmonary fibrosis in mice probably by up-regulating aerobic glycolysis via ROS to promote collagen production in fibroblasts.
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