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Gene expression analysis uncovers novel hedgehog interacting protein (HHIP) effects in human bronchial epithelial cells |
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| Authors: | Xiaobo Zhou Weiliang Qiu J. Fah Sathirapongsasuti Michael H. Cho John D. Mancini Taotao Lao Derek M. Thibault Augusto A. Litonjua Per S. Bakke Amund Gulsvik David A. Lomas Terri H. Beaty Craig P. Hersh Christopher Anderson Ute Geigenmuller Benjamin A. Raby Stephen I. Rennard Mark A. Perrella Edwin K. Silverman |
| Affiliation: | 1. Channing Division of Network Medicine, Department of Medicine, Brigham and Women''s Hospital, Boston, MA, USA;2. Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women''s Hospital, Boston, MA, USA;3. Harvard Medical School, Boston, MA, USA;4. Department of Biostatistics and Computational Biology, Dana-Faber Cancer Institute, Boston, MA, USA;5. Department of Biostatistics, Harvard School of Public Health, Boston, MA, USA;6. Dept of Thoracic Medicine, University of Bergen, Bergen, Norway;7. Department of Respiratory Medicine, University of Bergen, Bergen, Norway;8. Haukeland University Hospital, N-5021 Bergen, Norway;9. Department of Medicine, University of Cambridge, Cambridge Institute for Medical Research, Cambridge, UK;10. Johns Hopkins School of Public Health, Baltimore, MD, USA;11. Pulmonary and Critical Care Medicine, Nebraska Medical Center, Omaha, NE, USA;12. Newborn Medicine, Brigham and Women''s Hospital, Boston, MA, USA |
| Abstract: | Hedgehog interacting protein (HHIP) was implicated in chronic obstructive pulmonary disease (COPD) by genome-wide association studies (GWAS). However, it remains unclear how HHIP contributes to COPD pathogenesis. To identify genes regulated by HHIP, we performed gene expression microarray analysis in a human bronchial epithelial cell line (Beas-2B) stably infected with HHIP shRNAs. HHIP silencing led to differential expression of 296 genes; enrichment for variants nominally associated with COPD was found. Eighteen of the differentially expressed genes were validated by real-time PCR in Beas-2B cells. Seven of 11 validated genes tested in human COPD and control lung tissues demonstrated significant gene expression differences. Functional annotation indicated enrichment for extracellular matrix and cell growth genes. Network modeling demonstrated that the extracellular matrix and cell proliferation genes influenced by HHIP tended to be interconnected. Thus, we identified potential HHIP targets in human bronchial epithelial cells that may contribute to COPD pathogenesis. |
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