Expression analysis of asthma candidate genes during human and murine lung development

Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Respiratory research (Impact Factor: 3.09). 06/2011; 12(1):86. DOI: 10.1186/1465-9921-12-86
Source: PubMed


Little is known about the role of most asthma susceptibility genes during human lung development. Genetic determinants for normal lung development are not only important early in life, but also for later lung function.
To investigate the role of expression patterns of well-defined asthma susceptibility genes during human and murine lung development. We hypothesized that genes influencing normal airways development would be over-represented by genes associated with asthma.
Asthma genes were first identified via comprehensive search of the current literature. Next, we analyzed their expression patterns in the developing human lung during the pseudoglandular (gestational age, 7-16 weeks) and canalicular (17-26 weeks) stages of development, and in the complete developing lung time series of 3 mouse strains: A/J, SW, C57BL6.
In total, 96 genes with association to asthma in at least two human populations were identified in the literature. Overall, there was no significant over-representation of the asthma genes among genes differentially expressed during lung development, although trends were seen in the human (Odds ratio, OR 1.22, confidence interval, CI 0.90-1.62) and C57BL6 mouse (OR 1.41, CI 0.92-2.11) data. However, differential expression of some asthma genes was consistent in both developing human and murine lung, e.g. NOD1, EDN1, CCL5, RORA and HLA-G. Among the asthma genes identified in genome wide association studies, ROBO1, RORA, HLA-DQB1, IL2RB and PDE10A were differentially expressed during human lung development.
Our data provide insight about the role of asthma susceptibility genes during lung development and suggest common mechanisms underlying lung morphogenesis and pathogenesis of respiratory diseases.

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    • "Importantly, this correlates with a decrease in GSTCD at the mRNA level between these same developmental stages, as revealed by mining and specifically analysing the results of a study previously reported by Melén et al. [23]. That protein and mRNA levels of GSTCD are relatively higher in the pseudoglandular stage when compared with the canalicular stage is significant as it is through this stage of development that airway smooth muscle cells, mast cells, T-lymphocytes and dendritic cells all begin to appear within the lung parenchyma [23]. Conversely, the reduction in GSTCD in the canalicular phase coincides with alteration of the epithelium and the surrounding mesenchyme. "
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    • "Interestingly, Alox15 is also involved in the modulation of neuronal function such as in axon pathfinding, in particular at the level of the growth cones [58] and in the neuronal protection and survival after axotomy [59]. The Robo1 (roundabout 1) gene encodes for a membrane receptor and it is expressed both in non-neural tissue (lung and kidney [60,61]) and, more abundantly, in the nervous system (brain, retina and spinal cord), where it plays a pivotal role in axon pathfinding, particularly during the process of midline crossing in the developing spinal cord and hindbrain [62–67]. Since microarray experiments indicated an increased level of the Alox15 and Robo1 mRNA, we asked whether they were actually translated into proteins in spinal cultures; that is, we wondered whether interfacing cells with MWCNT platforms affected also their protein level. "
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    • "Publically available data [22,23] were utilized to see whether HTR4 was differentially expressed during normal human lung development. Previously, human fetal lung tissues were obtained from National Institute of Child Health and Human Development tissue databases and microarray profiled to investigate the expression spanning different gestational ages. "
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