Dataset Information

Gene expression profiling identifies MMP-12 and ADAMDEC1 as potential pathogenic mediators of pulmonary sarcoidosis.

ABSTRACT:

Rationale

Little is known about the genetic regulation of granulomatous inflammation in sarcoidosis.

Objectives

To determine if tissue gene array analysis would identify novel genes engaged in inflammation and lung remodeling in patients with sarcoidosis.

Methods

Gene expression analysis was performed on tissues obtained from patients with sarcoidosis at the time of diagnosis (untreated) (n = 6) compared with normal lung tissue (n = 6). Expression of select genes was further confirmed in lung tissue from a second series of patients with sarcoidosis and disease-free control subjects (n = 11 per group) by semi-quantitative RT-PCR. Interactive gene networks were identified in patients with sarcoidosis using Ingenuity Pathway Analysis (Ingenuity Systems, Inc., Redwood, CA) software. The expression of proteins corresponding to selected overexpressed genes was determined using fluorokine multiplex analysis, and immunohistochemistry. Selected genes and proteins were then analyzed in bronchoalveolar lavage fluid in an independent series of patients with sarcoidosis (n = 36) and control subjects (n = 12).

Measurements and main results

A gene network engaged in Th1-type responses was most significantly overexpressed in the sarcoidosis lung tissues, including genes not previously reported in the context of sarcoidosis (e.g., IL-7). MMP-12 and ADAMDEC1 transcripts were most highly expressed (> 25-fold) in sarcoidosis lung tissues, corresponding with increased protein expression by immunohistochemistry. MMP-12 and ADAMDEC1 gene and protein expression were increased in bronchoalveolar lavage samples from patients with sarcoidosis, correlating with disease severity.

Conclusions

Tissue gene expression analyses provide novel insights into the pathogenesis of pulmonary sarcoidosis. MMP-12 and ADAMDEC1 emerge as likely mediators of lung damage and/or remodeling and may serve as markers of disease activity.

SUBMITTER: Crouser ED

PROVIDER: S-EPMC2684019 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature

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Publications

Gene expression profiling identifies MMP-12 and ADAMDEC1 as potential pathogenic mediators of pulmonary sarcoidosis.

Crouser Elliott D ED Culver Daniel A DA Knox Kenneth S KS Julian Mark W MW Shao Guohong G Abraham Susamma S Liyanarachchi Sandya S Macre Jennifer E JE Wewers Mark D MD Gavrilin Mikhail A MA Ross Patrick P Abbas Abbas A Eng Charis C

American journal of respiratory and critical care medicine 20090212 10

<h4>Rationale</h4>Little is known about the genetic regulation of granulomatous inflammation in sarcoidosis.<h4>Objectives</h4>To determine if tissue gene array analysis would identify novel genes engaged in inflammation and lung remodeling in patients with sarcoidosis.<h4>Methods</h4>Gene expression analysis was performed on tissues obtained from patients with sarcoidosis at the time of diagnosis (untreated) (n = 6) compared with normal lung tissue (n = 6). Expression of select genes was furthe ...[more]

PMID: 19218196

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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

Gene expression profiling identifies MMP-12 and ADAMDEC1 as potential pathogenic mediators of pulmonary sarcoidosis.

Rationale

Objectives

Methods

Measurements and main results

Conclusions

Publications

Gene expression profiling identifies MMP-12 and ADAMDEC1 as potential pathogenic mediators of pulmonary sarcoidosis.

Similar Datasets

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