Chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) are chronic progressive lung diseases with rising mortality rates in the United States. Epidemiological studies have revealed sex-specific trends in the prevalence and mortality of these diseases, such that more males are afflicted with IPF whereas the burden of COPD is higher in females. These observations suggest that cellular and molecular mechanisms driving the development and severity of COPD and IPF are not fully conserved between sexes. Modulated expression of a number of genes related to immune regulation and extracellular matrix remodeling- both important events involved in IPF and COPD- have been measured in lung cells and tissues; however, limited investigations have probed the expression of genes related to steroid hormone signaling between men and women. We hypothesized that the expression of sex steroid receptors and metabolizing enzymes will differ by gender and disease. To elucidate immune-, extracellular matrix (ECM)- and hormonally-related genes that are differentially expressed by gender in human control and diseased lung tissues, we employed custom-designed gene arrays to measure the transcriptional expression of 48 genes (39 immune- and ECM-relevant genes and 9 sex-related genes) simultaneously by quantitative real-time PCR (qRT-PCR) methodology.
Gene profiles were generated for 36 lung tissue samples obtained from control individuals, as well as males and females diagnosed with mild COPD and mild and medium severity IPF based on percent forced vital capacity (%FVC). Results reveal a number of genes that show trends of differential expression among sexes, disease type, and disease severity. A number of genes revealed by this work are potentially play a role in these observations and can now be investigated further. Estrogen and androgen receptors and a number of immune and ECM genes (COX2, CCR3, IL1-RN, I-6, MMP7, SPP1, MMP12, and MUC1) displayed variable expression trends by disease and gender. The factors that contribute to differential expression of these targets between males and females is not known but it is possible that estrogen and androgen hormones regulate some of the immune and ECM targets. These results show, for the first time, differential expression of hormone receptors among human control and diseased lung tissue as well as altered expression between males and females. Furthermore, this study elucidates expression patterns of several immune/matrix-remodeling genes that are distinct to disease and sex.
Overall, this work highlights genes that may contribute to gender trends observed for lung diseases and are potential targets for future research. These results increase our basic understanding of the molecular mechanisms involved in 2 distinct lung diseases. Our findings may also aid in the development of future therapeutics as well as enhance our understanding of potential risk factors and predispositions for obstructive and restrictive lung diseases.
|Advisor:||Sabo-Attwood, Tara L.|
|Commitee:||Karmaus, Wilfried, Volz, David, Zhang, Hongmei|
|School:||University of South Carolina|
|Department:||Environmental Health Sciences|
|School Location:||United States -- South Carolina|
|Source:||MAI 49/01M, Masters Abstracts International|
|Subjects:||Molecular biology, Environmental Health|
|Keywords:||Chronic obstructive pulmonary disease, Fibrosis, Gene expression|
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