@article{483de81aa4304b06982e3203a81d4260,
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.",
keywords = "COPD (Chronic obstructive pulmonary disease), Extracellular matrix (ECM), Gene expression profiling, Hedgehog interacting protein (HHIP), Network modeling",
author = "Xiaobo Zhou and Weiliang Qiu and Sathirapongsasuti, {J. Fah} and Cho, {Michael H.} and Mancini, {John D.} and Taotao Lao and Thibault, {Derek M.} and Litonjua, {Augusto A.} and Bakke, {Per S.} and Amund Gulsvik and Lomas, {David A.} and Beaty, {Terri H.} and Hersh, {Craig P.} and Christopher Anderson and Ute Geigenmuller and Raby, {Benjamin A.} and Rennard, {Stephen I.} and Perrella, {Mark A.} and Choi, {Augustine M.K.} and John Quackenbush and Silverman, {Edwin K.}",
note = "Funding Information: The National Emphysema Treatment Trial was supported by the National Heart, Lung, and Blood Institute contracts N01HR76101, N01HR76102, N01HR76103, N01HR76104, N01HR76105, N01HR76106, N01HR76107, N01HR76108, N01HR76109, N01HR76110, N01HR76111, N01HR76112, N01HR76113, N01HR76114, N01HR76115, N01HR76116, N01HR76118 and N01HR76119. Funding Information: This work was supported by the U.S. National Institutes of Health (NIH) grants R01 HL075478 , R01 HL084323 , P01 HL083069 , P01 HL105339 , U01 HL089856 (Silverman), U01 HL089897 , and P01 H105339 . The National Emphysema Treatment Trial was supported by the National Heart, Lung, and Blood Institute, the Centers for Medicare and Medicaid Services and the Agency for Healthcare Research and Quality. The Normative Aging Study is supported by the Cooperative Studies Program/ERIC of the US Department of Veterans Affairs and is a component of the Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC). The Norway GenKOLS study (Genetics of Chronic Obstructive Lung Disease, GSK code RES11080), the ECLIPSE study (clinicaltrials.gov identifier NCT00292552; GSK code SCO104960) and the ICGN study are funded by GlaxoSmithKline. The COPDGene project is also supported by the COPD Foundation through contributions made by an Industry Advisory Board comprised of AstraZeneca, Boehringer Ingelheim, Novartis, Pfizer and Sunovion. This study used biological specimens and data provided by the Lung Tissue Research Consortium (LTRC) supported by the National Heart, Lung, and Blood Institute (NHLBI). ",
year = "2013",
month = may,
doi = "10.1016/j.ygeno.2013.02.010",
language = "English (US)",
volume = "101",
pages = "263--272",
journal = "Genomics",
issn = "0888-7543",
publisher = "Academic Press Inc.",
number = "5",
}