Downregulated sphingolipid metabolism in idiopathic pulmonary fibrosis (IPF) lungs. Downregulated sphingolipid metabolism in idiopathic pulmonary fibrosis (IPF)

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Downregulated sphingolipid metabolism in idiopathic pulmonary fibrosis (IPF) lungs. Downregulated sphingolipid metabolism in idiopathic pulmonary fibrosis (IPF) lungs. (A) Data for metabolic intermediates in the normal lung (NL) are shown in green boxes and data for IPF are represented in purple. Quantities are in arbitrary units specific to the internal standards for each quantified metabolite and normalised to protein concentration (n=8 for each box). Samples of patients with IPF exhibited lower levels of sphinganine, sphingosine and sphingomyelin. (B) The classical sphingolipid is shown. (C) Analysis of gene expression for key enzymes of the sphingolipids metabolism; data for control lung are shown in open blue boxes and data for IPF lung are represented in open green boxes (y-axis label of metabolic changes is shown as counts×106). The genes encoding sphingosine 1-phosphate (S1P) metabolic pathway showed downregulated sphingomyelinase (SMPD1 and SMPD4) as well as downregulated delta(4)-desaturase, sphingolipid 1 (DEGS1), suggesting a reduced ceramide production, and downregulated ACER3 (alkaline ceramidase 3) indicates reduced sphingosine and S1P production. Genes encoding DEGS1 (p=1.25e−10), ACER3 (p=2.08e−7), SMPD1 (p=2e−6) and SMPD4 (p=6.67e−14) were significantly changed in IPF lungs compared with normal (y-axis label for gene expression encoding enzymes is shown as fold changes of relative RNA levels of enzymes). Yidan D Zhao et al. BMJ Open Resp Res 2017;4:e000183 ©2017 by British Thoracic Society