Abstract
Altered lipid metabolism has been associated to cystic fibrosis disease, which is characterized by chronic lung inflammation and various organs dysfunction. Here, we present the validation of an untargeted lipidomics approach based on high-resolution mass spectrometry aimed at identifying those lipid species that unequivocally sign CF pathophysiology. Of n.13375 mass spectra recorded on cystic fibrosis bronchial epithelial airways epithelial cells IB3, n.7787 presented the MS/MS data, and, after software and manual validation, the final number of annotated lipids was restricted to n.1159. On these lipids, univariate and multivariate statistical approaches were employed in order to select relevant lipids for cellular phenotype discrimination between cystic fibrosis and HBE healthy cells. In cystic fibrosis IB3 cells, a pervasive alteration in the lipid metabolism revealed changes in the classes of ether-linked phospholipids, cholesterol esters, and glycosylated sphingolipids. Through functions association, it was evidenced that lipids variation involves the moiety implicated in membrane composition, endoplasmic reticulum, mitochondria compartments, and chemical and biophysical lipids properties. This study provides a new perspective in understanding the pathogenesis of cystic fibrosis and strengthens the need to use a validated mass spectrometry-based lipidomics approach for the discovery of potential biomarkers and perturbed metabolism.
Highlights
Lipids are a fundamental component of cellular membranes and signaling molecules regulating cellular functions that include energy storage, cell proliferation and death, stress response, and inflammation
Targeted methods are a high-sensitive analysis dedicated to the identification and quantification of known classes of lipids, whereas nontargeted methods, usually employing high-resolution mass spectrometry, aim to identify and semi-quantify every likely lipid species contained in the samples [3,4,5]
We present a novel lipidomics approach aimed at identifying those lipid species that unequivocally sign cystic fibrosis (CF) pathophysiology
Summary
Lipids are a fundamental component of cellular membranes and signaling molecules regulating cellular functions that include energy storage, cell proliferation and death, stress response, and inflammation. Targeted methods are a high-sensitive analysis dedicated to the identification and quantification of known classes of lipids, whereas nontargeted methods, usually employing high-resolution mass spectrometry, aim to identify and semi-quantify every likely lipid species contained in the samples [3,4,5] Employing this technique, different tasks can be performed: (1) characterization, identification, and quantification of specific lipid species known to be related to pathological events, and (2) identification of new prognostic or diagnostic biomarkers able to discriminate with higher specificity and sensitivity the healthy phenotype from the pathological ones. CF is a pulmonary disease caused by different mutations in the gene for the chloride/carbonate channel CFTR These mutations are responsible for dysregulation in the electrolytic equilibrium within the protective mucus of respiratory airways, leading to lung chronic inflammation and infections, together with pancreatic insufficiency and multiple organs dysfunction [7].
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