Dataset Information

Novel protein pathways in development and progression of pulmonary sarcoidosis.

ABSTRACT: 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.

SUBMITTER: Bhargava M

PROVIDER: S-EPMC7413390 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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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:PurposeReduced physical activity in many chronic diseases is consistently associated with increased morbidity. Little is known about physical activity in sarcoidosis. The aim of this study was to objectively assess physical activity in patients with pulmonary sarcoidosis and investigate its relationship with lung function, exercise capacity, symptom burden, and health status.MethodsPhysical activity was assessed over one week in 15 patients with pulmonary sarcoidosis and 14 age-matched healthy controls with a tri-axial accelerometer (ActivPal™) and the International Physical Activity Questionnaire (IPAQ). All participants underwent pulmonary function tests, 6-min walk test (6MWT) and completed the Fatigue Assessment Scale (FAS), Medical Research Council (MRC) Dyspnoea Scale and the King's Sarcoidosis Questionnaire (KSQ).ResultsPatients with sarcoidosis had significantly lower daily step counts than healthy controls; mean (SD) 5624 (1875) versus 10,429 (2942) steps (p?<?0.01) and a trend towards fewer sit-to-stand transitions each day (p?=?0.095). Only two patients (13%) self-reported undertaking vigorous physical activity (IPAQ) compared to half of healthy individuals (p?<?0.01). Daily step count was significantly associated with 6MWT distance in sarcoidosis (r?=?0.634, p?=?0.01), but not with forced vital capacity (r?=?0.290), fatigue (r?=?0.041), dyspnoea (r?=?-0.466) or KSQ health status (r?=?0.099-0.484). Time spent upright was associated with fatigue (r?=?-0.630, p?=?0.012) and health status (KSQ Lung scores r?=?0.524, p?=?0.045), and there was a significant correlation between the number of sit-to-stand transitions and MRC dyspnoea score (r?=?-0.527, p?=?0.044).ConclusionPhysical activity is significantly reduced in sarcoidosis and is associated with reduced functional exercise capacity (6MWD). Fatigue, exertional symptoms and health status were more closely associated with time spent upright and the number of bouts of physical activity, as compared to step counts. Further studies are warranted to identify the factors that determine different physical activity profiles in sarcoidosis.

Dataset Information

Novel protein pathways in development and progression of pulmonary sarcoidosis.

Publications

Novel protein pathways in development and progression of pulmonary sarcoidosis.

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