Gene expression analysis uncovers novel hedgehog interacting protein (HHIP) effects in human bronchial epithelial cells

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, Augustine M.K. Choi, John QuackenbushEdwin K. Silverman

Research output: Contribution to journalArticle

29 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)263-272
Number of pages10
JournalGenomics
Volume101
Issue number5
DOIs
StatePublished - May 2013

Keywords

  • COPD (Chronic obstructive pulmonary disease)
  • Extracellular matrix (ECM)
  • Gene expression profiling
  • Hedgehog interacting protein (HHIP)
  • Network modeling

ASJC Scopus subject areas

  • Genetics

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    Zhou, X., Qiu, W., Sathirapongsasuti, J. F., Cho, M. H., Mancini, J. D., Lao, T., Thibault, D. M., Litonjua, A. A., Bakke, P. S., Gulsvik, A., Lomas, D. A., Beaty, T. H., Hersh, C. P., Anderson, C., Geigenmuller, U., Raby, B. A., Rennard, S. I., Perrella, M. A., Choi, A. M. K., ... Silverman, E. K. (2013). Gene expression analysis uncovers novel hedgehog interacting protein (HHIP) effects in human bronchial epithelial cells. Genomics, 101(5), 263-272. https://doi.org/10.1016/j.ygeno.2013.02.010