A metabolomic approach shows sphingosine 1-phosphate and lysophospholipids as mediators of the therapeutic effect of liver growth factor in emphysema.
Tobacco smoke exposure is the principal cause of lung tissue destruction, which in turn results in emphysema that leads into shortness of breath. Liver growth factor (LGF, a cell and tissue regenerating factor with therapeutic activity in several organs) has antifibrotic and antioxidant properties that could be useful to promote lung tissue regenerating capacity in damaged lungs. The current study has examined differences in metabolite profiles (fingerprints) of plasma from mice (strain C57BL/6J, susceptible to develop emphysema) exposed to tobacco smoke during six months. One group of mice received a treatment with Liver Growth Factor (LGF) after emphysema was established, whereas the other group did not receive the treatment. Age and sex-matched mice not exposed to smoke were also maintained with or without treatment as controls. Metabolic fingerprints (untargeted analysis) of plasma after protein precipitation were obtained by LC-QTOF-MS. The signals were processed and a large number of possible metabolites were found (23944). Multivariate data analysis provided models that highlighted the differences between control and smoke exposed mice in both conditions. Accurate masses of features (possible compounds) representing significant differences were searched using online public databases. Lipid mediators, related to intracellular signaling in inflammation, were found among the metabolites putatively identified as markers of the different conditions and among them, sphingosine, sphingosine 1-phosphate and lysophospholipids point at the relevance of such metabolites in the regulation of the processes related to tissue regeneration mediated by LGF. These results also suggest that metabolomic fingerprinting could potentially guide the characterization of relevant metabolites leading the regeneration of lungs in emphysema disease.
CEMBIO (Center for Metabolomics and Bioanalysis), Facultad de Farmacia, Universidad CEU San Pablo, Campus Montepríncipe, Boadilla del Monte, 28668, Madrid, Spain.
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Navarrete
CEMBIO (Center for Metabolomics and Bioanalysis), Facultad de Farmacia, Universidad CEU San Pablo, Campus Montepríncipe, Boadilla del Monte, 28668, Madrid, Spain.
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Rupérez
CEMBIO (Center for Metabolomics and Bioanalysis), Facultad de Farmacia, Universidad CEU San Pablo, Campus Montepríncipe, Boadilla del Monte, 28668, Madrid, Spain.
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Mendes
Pulmonology Experimental Lab., IIS-Fundación Jiménez Díaz-UAM-CIBERES, Avenida Reyes Católicos 2, 28040, Madrid, Spain.
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Pérez-Rial
Pulmonology Experimental Lab., IIS-Fundación Jiménez Díaz-UAM-CIBERES, Avenida Reyes Católicos 2, 28040, Madrid, Spain.
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Girón-Martínez
Pulmonology Experimental Lab., IIS-Fundación Jiménez Díaz-UAM-CIBERES, Avenida Reyes Católicos 2, 28040, Madrid, Spain.
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Terrón-Expósito
Pulmonology Experimental Lab., IIS-Fundación Jiménez Díaz-UAM-CIBERES, Avenida Reyes Católicos 2, 28040, Madrid, Spain.
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Díaz-Gil
Pulmonology Experimental Lab., IIS-Fundación Jiménez Díaz-UAM-CIBERES, Avenida Reyes Católicos 2, 28040, Madrid, Spain.
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Peces-Barba
CEMBIO (Center for Metabolomics and Bioanalysis), Facultad de Farmacia, Universidad CEU San Pablo, Campus Montepríncipe, Boadilla del Monte, 28668, Madrid, Spain.
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Barbas
CEMBIO (Center for Metabolomics and Bioanalysis), Facultad de Farmacia, Universidad CEU San Pablo, Campus Montepríncipe, Boadilla del Monte, 28668, Madrid, Spain. Electronic address: antogar@ceu.es.
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García
D000818:Animals; D001663:Bilirubin / Q000494:pharmacology / Q000627:therapeutic use*; D019570:Inhalation Exposure / Q000009:adverse effects; D008246:Lysophospholipids / Q000378:metabolism*; D008297:Male; D055432:Metabolomics / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D011656:Pulmonary Emphysema / Q000188:drug therapy / Q000378:metabolism*; D012709:Serum Albumin / Q000494:pharmacology / Q000627:therapeutic use*; D000075462:Serum Albumin, Human; D012907:Smoking / Q000009:adverse effects* / Q000188:drug therapy; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism
D008246:Lysophospholipids; D012709:Serum Albumin; C053498:albumin-bilirubin complex; C060506:sphingosine 1-phosphate; D013110:Sphingosine; D001663:Bilirubin; D000075462:Serum Albumin, Human
COPD; Emphysema; LC–MS; LGF; Metabolomics; Tobacco exposure