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首页> 外文期刊>Genomics >Gene expression analysis uncovers novel hedgehog interacting protein (HHIP) effects in human bronchial epithelial cells
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Gene expression analysis uncovers novel hedgehog interacting protein (HHIP) effects in human bronchial epithelial cells

机译：基因表达分析揭示了人类支气管上皮细胞中的新型刺猬相互作用蛋白（HHIP）作用

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摘要

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.
机译：通过全基因组关联研究（GWAS），刺猬相互作用蛋白（HHIP）与慢性阻塞性肺疾病（COPD）有关。但是，尚不清楚HHIP如何促进COPD发病机理。为了鉴定受HHIP调控的基因，我们在稳定感染了HHIP shRNA的人支气管上皮细胞系（Beas-2B）中进行了基因表达微阵列分析。 HHIP沉默导致296个基因的差异表达;发现了与COPD名义上相关的变体的富集。通过实时PCR在Beas-2B细胞中验证了18个差异表达基因。在人类COPD和对照肺组织中测试的11个经过验证的基因中有7个表现出明显的基因表达差异。功能注释表明细胞外基质和细胞生长基因富集。网络建模表明受HHIP影响的细胞外基质和细胞增殖基因倾向于相互联系。因此，我们在人支气管上皮细胞中确定了潜在的HHIP靶标，这些靶标可能有助于COPD发病机理。

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