RNA sequencing in human HepG2 hepatocytes reveals PPAR-α mediates transcriptome responsiveness of bilirubin
RNA sequencing in human HepG2 hepatocytes reveals PPAR-α mediates transcriptome responsiveness of bilirubin
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DOI：
10.1152/physiolgenomics.00028.2019
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发表时间：
2019-06-01
影响因子：
4.6
通讯作者：
Hinds, Terry D., Jr.
中科院分区：
文献类型：
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作者：
Gordon, Darren M.;Blomquist, Thomas M.;Hinds, Terry D., Jr.
胆红素是一种有效的抗氧化剂，可以减少炎症和脂肪的积累。有报道称，胆红素的基因反应主要归因于其抗氧化功能。使用RNA测序，我们发现，胆绿素，这是迅速还原为胆红素，诱导转录组反应，在人类HepG 2肝细胞中的过氧化物酶体增殖物激活受体（PPAR）-α依赖的方式（398个基因与>2倍的变化;错误发现率P < 0.05）。为了比较，当通过慢病毒shRNA敲低抑制PPAR-alpha时，一组更窄的基因表现出差异表达（23个基因）。基因集富集分析显示，拟南芥红蛋白-PPAR-α转录组介导氧化还原过程、线粒体功能、对营养素的反应、脂肪酸氧化和脂质稳态的途径。总之，这些发现表明，胆红素产生的转录组反应主要是PPAR-alpha依赖性的，其抗氧化功能调节了一小部分基因。
Bilirubin is a potent antioxidant that reduces inflammation and the accumulation of fat. There have been reports of gene responses to bilirubin, which was mostly attributed to its antioxidant function. Using RNA sequencing, we found that biliverdin, which is rapidly reduced to bilirubin, induced transcriptome responses in human HepG2 hepatocytes in a peroxisome proliferator-activated receptor (PPAR)-alpha-dependent fashion (398 genes with >2-fold change; false discovery rate P < 0.05). For comparison, a much narrower set of genes demonstrated differential expression when PPAR-alpha was suppressed via lentiviral shRNA knockdown (23 genes). Gene set enrichment analysis revealed the bilirubin-PPAR-alpha transcriptome mediates pathways for oxidation-reduction processes, mitochondrial function, response to nutrients, fatty acid oxidation, and lipid homeostasis. Together, these findings suggest that transcriptome responses from the generation of bilirubin are mostly PPAR-alpha dependent, and its antioxidant function regulates a smaller set of genes.