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 Quackenbush, Edwin K Silverman, 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 Quackenbush, Edwin K Silverman
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.
Trial registration: ClinicalTrials.gov NCT00292552.
Conflict of interest statement
Competing Interests Statement:
E.K.S. has received grant support and consulting and speaker’s fees from GlaxoSmithKline, consulting and speaker’s fees from Astra-Zeneca, and consulting fees from Merck. X.Z., W.Q., M.H.C., J.F.S., J.D.M., T.L., D.M.T, G.L., P.S.B., A.G., D.A.L., T.H.B., C.P.H., C.A., U.G., B.A.R., S.I.R., M.A.P., A.M.K.C. and J.Q. do not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript.
Copyright © 2013 Elsevier Inc. All rights reserved.
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Source: PubMed