Dataset Information

Novel Protein Pathways in Development and Progression of Pulmonary Sarcoidosis.

ABSTRACT: Sarcoidosis is a disease that affects multiple organ systems, with lung disease seen commonly and is the most frequent cause of sarcoidosis-related mortality. We investigated to compare protein expression in the lung from both bronchoalveolar lavage fluid (BAL) cells and fluid (BALF) in newly diagnosed patients with sarcoidosis. Mass spectral data acquisition was conducted on an Orbitrap Fusion instrument in data-dependent mode using either label-free (BALF) or label-based (intracellular) approach. We identified 4,306 high confidence intracellular proteins (probability >99%) with 272 differentially expressed proteins controlling for an FDR 5%. The protein map to several known canonical pathways including phagosome maturation, clathrin-mediated endocytic signaling, NRF-2 mediated oxidant stress response, The examination of BALF identified 1,192 proteins, xxx and xxx protein with differential expression between controls vs. sarcoidosis and progressive vs. non-progressive sarcoidosis respectively. Several of the proteins identified mapping to the differentially expressed proteins were also detected in the BALF.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Bronchoalveolar Lavage

DISEASE(S): Sarcoidosis

SUBMITTER: Kevin Viken

LAB HEAD: Maneesh Bhargava

PROVIDER: PXD014438 | Pride | 2021-09-08

REPOSITORIES: Pride

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			Action	DRS
	bharg005_kviken_20190207_17199_14258_rep_01.raw	Raw
	bharg005_kviken_20190207_17199_14258_rep_02.raw	Raw
	bharg005_kviken_20190207_17199_14258_rep_03.raw	Raw
	bharg005_kviken_20190207_17199_18254_rep_01.raw	Raw
	bharg005_kviken_20190207_17199_18254_rep_02.raw	Raw

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Novel protein pathways in development and progression of pulmonary sarcoidosis.

Bhargava Maneesh M Viken K J KJ Barkes B B Griffin T J TJ Gillespie M M Jagtap P D PD Sajulga R R Peterson E J EJ Dincer H E HE Li L L Restrepo C I CI O'Connor B P BP Fingerlin T E TE Perlman D M DM Maier L A LA

Scientific reports 20200806 1

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 n ...[more]

PMID: 32764642

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Project description:Background: Sarcoidosis and idiopathic pulmonary fibrosis (IPF) are two most frequent forms of interstitial lung diseases (ILDs). Cellular and biochemical composition of bronchoalveolar lavage fluid (BALf) was shown to reflect the proliferative and fibrotic changes in the local environment in the lung. However, the usefulness of BALf cellular profile evaluation in the diagnosis of ILDs is limited. The aim of the study was a multivariate, molecular, comparative analysis of BALf cells from IPF and sarcoidosis patients. Methods: Transcriptomic measurements were carried out using Affymetrix Human Gene 2.1 ST ArrayStrip in 21 samples: 9 IPF and 12 sarcoidosis. The mRNA expression for the most significantly differentiating genes was evaluated by real time PCR in 32 samples (11 IPF and 21 sarcoidosis). Results: The number of genes differentially expressed between IPF and sarcoidosis groups were 4832 (13359 probesets). Our cluster analysis indicated that sarcoidosis BALf cells are characterized by increased mRNA expression of genes associated with ribosome biogenesis, transcription machinery. Clusters formed by genes with changed mRNA expression in IPF samples were implicated in the processes of cell adhesion and migration, metalloproteinase expression and negative regulation of cell proliferation. PCR verification showed higher expression of ANK3 in the sarcoidosis compared to the IPF group, and higher expression of MMP7 and PPBP in patients with IPF. The GO analysis indicated that predominant biological processes associated with the differential mRNA gene expression of BALf cells were upregulation of neutrophils in IPF and lymphocytes in sarcoidosis. Conclusions: Analysis of BALf from sarcoidosis and IPF showed highly different mRNA profile of cells present in bronchoalveolar compartment and provided new data on the pathobiology of these ILDs. The changes of most important biological processes observed at the molecular level in BALf cells were associated with ribosome biogenesis and proteasome apparatus in sarcoidosis and neutrophilic dysfunction in IPF.