Novel protein pathways in development and progression of pulmonary sarcoidosis.

Autor: Bhargava M; Division of Pulmonary, Critical Care and Sleep Medicine, University of Minnesota, MMC 276, 420 Delaware St SE, Minneapolis, MN, USA. bharg005@umn.edu., Viken KJ; Division of Pulmonary, Critical Care and Sleep Medicine, University of Minnesota, MMC 276, 420 Delaware St SE, Minneapolis, MN, USA., Barkes B; Division of Environmental and Occupational Health Sciences, National Jewish Health, Denver, CO, USA., Griffin TJ; Biochemistry, Molecular Biology and Biophysics, College of Biological Sciences, University of Minnesota, Minneapolis, MN, USA., Gillespie M; Division of Environmental and Occupational Health Sciences, National Jewish Health, Denver, CO, USA., Jagtap PD; Biochemistry, Molecular Biology and Biophysics, College of Biological Sciences, University of Minnesota, Minneapolis, MN, USA., Sajulga R; Biochemistry, Molecular Biology and Biophysics, College of Biological Sciences, University of Minnesota, Minneapolis, MN, USA., Peterson EJ; Center for Immunology, University of Minnesota, Minneapolis, MN, USA., Dincer HE; Division of Pulmonary, Critical Care and Sleep Medicine, University of Minnesota, MMC 276, 420 Delaware St SE, Minneapolis, MN, USA., Li L; Division of Environmental and Occupational Health Sciences, National Jewish Health, Denver, CO, USA., Restrepo CI; Division of Environmental and Occupational Health Sciences, National Jewish Health, Denver, CO, USA., O'Connor BP; Center for Genes, Environment and Health, National Jewish Health, Denver, CO, USA., Fingerlin TE; Center for Genes, Environment and Health, National Jewish Health, Denver, CO, USA., Perlman DM; Division of Pulmonary, Critical Care and Sleep Medicine, University of Minnesota, MMC 276, 420 Delaware St SE, Minneapolis, MN, USA., Maier LA; Division of Environmental and Occupational Health Sciences, National Jewish Health, Denver, CO, USA.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2020 Aug 06; Vol. 10 (1), pp. 13282. Date of Electronic Publication: 2020 Aug 06.
DOI: 10.1038/s41598-020-69281-8
Abstrakt: Pulmonary involvement occurs in up to 95% of sarcoidosis cases. In this pilot study, we examine lung compartment-specific protein expression to identify pathways linked to development and progression of pulmonary sarcoidosis. We characterized bronchoalveolar lavage (BAL) cells and fluid (BALF) proteins in recently diagnosed sarcoidosis cases. We identified 4,306 proteins in BAL cells, of which 272 proteins were differentially expressed in sarcoidosis compared to controls. These proteins map to novel pathways such as integrin-linked kinase and IL-8 signaling and previously implicated pathways in sarcoidosis, including phagosome maturation, clathrin-mediated endocytic signaling and redox balance. In the BALF, the differentially expressed proteins map to several pathways identified in the BAL cells. The differentially expressed BALF proteins also map to aryl hydrocarbon signaling, communication between innate and adaptive immune response, integrin, PTEN and phospholipase C signaling, serotonin and tryptophan metabolism, autophagy, and B cell receptor signaling. Additional pathways that were different between progressive and non-progressive sarcoidosis in the BALF included CD28 signaling and PFKFB4 signaling. Our studies demonstrate the power of contemporary proteomics to reveal novel mechanisms operational in sarcoidosis. Application of our workflows in well-phenotyped large cohorts maybe beneficial to identify biomarkers for diagnosis and prognosis and therapeutically tenable molecular mechanisms.
Databáze: MEDLINE
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