title: Gene expression analysis uncovers novel hedgehog interacting protein (HHIP) effects in human bronchial epithelial cells.
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.
authors: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA. Xiaobo.zhou@channing.harvard.edu
authors: Xiaobo
authors: X
authors: Zhou
authors: Weiliang
authors: W
authors: Qiu
authors: J Fah
authors: JF
authors: Sathirapongsasuti
authors: Michael H
authors: MH
authors: Cho
authors: John D
authors: JD
authors: Mancini
authors: Taotao
authors: T
authors: Lao
authors: Derek M
authors: DM
authors: Thibault
authors: Augusto A
authors: AA
authors: Litonjua
authors: Per S
authors: PS
authors: Bakke
authors: Amund
authors: A
authors: Gulsvik
authors: David A
authors: DA
authors: Lomas
authors: Terri H
authors: TH
authors: Beaty
authors: Craig P
authors: CP
authors: Hersh
authors: Christopher
authors: C
authors: Anderson
authors: Ute
authors: U
authors: Geigenmuller
authors: Benjamin A
authors: BA
authors: Raby
authors: Stephen I
authors: SI
authors: Rennard
authors: Mark A
authors: MA
authors: Perrella
authors: Augustine M K
authors: AM
authors: Choi
authors: John
authors: J
authors: Quackenbush
authors: Edwin K
authors: EK
authors: Silverman
mesh_terms: D001980:Bronchi / Q000378:metabolism / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D002460:Cell Line; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D055785:Gene Knockdown Techniques; D053263:Gene Regulatory Networks; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D058977:Molecular Sequence Annotation; D020411:Oligonucleotide Array Sequence Analysis; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D020545:Respiratory Mucosa / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction; D059467:Transcriptome; D015854:Up-Regulation
chemical_list: D002352:Carrier Proteins; D016326:Extracellular Matrix Proteins; C117596:HHIP protein, human; D008562:Membrane Glycoproteins; D034741:RNA, Small Interfering