Chenodeoxycholic Acid (CDCA) Promoted Intestinal Epithelial Cell Proliferation by Regulating Cell Cycle Progression and Mitochondrial Biogenesis in IPEC-J2 Cells

文献类型： 外文期刊

第一作者： Xu, Lei

作者： Xu, Lei;Li, Yanpin;Wei, Zixi;Bai, Rong;Gao, Ge;Sun, Wenjuan;Jiang, Xianren;Li, Xilong;Pi, Yu;Bai, Rong;Wang, Junjun

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关键词： chenodeoxycholic acid (CDCA); cell proliferation; cell cycle; mitochondria; IPEC-J2 cells

期刊名称：ANTIOXIDANTS （ 影响因子：7.675； 五年影响因子：7.886 ）

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年卷期： 2022 年 11 卷 11 期

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收录情况： SCI

摘要： Chenodeoxycholic acid (CDCA), a primary bile acid (BA), has been demonstrated to play an important role as a signaling molecule in various physiological functions. However, the role of CDCA in regulating intestinal epithelial cell (IEC) function remains largely unknown. Herein, porcine intestinal epithelial cells (IPEC-J2) were used as an in vitro model to investigate the effects of CDCA on IEC proliferation and explore the underlying mechanisms. IPEC-J2 cells were treated with CDCA, and flow cytometry and transcriptome analysis were adopted to investigate the effects and potential molecular mechanisms of CDCA on the proliferation of IECs. Our results indicated that adding 50 mu mol/L of CDCA in the media significantly increased the proliferation of IPEC-J2 cells. In addition, CDCA treatment also hindered cell apoptosis, increased the proportion of G0/G1 phase cells in the cell cycle progression, reduced intracellular ROS, and MDA levels, and increased mitochondrial membrane potential, antioxidation enzyme activity (T-AOC and CAT), and intracellular ATP level (p < 0.05). RNA-seq results showed that CDCA significantly upregulated the expression of genes related to cell cycle progression (Cyclin-dependent kinase 1 (CDK1), cyclin G2 (CCNG2), cell-cycle progression gene 1 (CCPG1), Bcl-2 interacting protein 5 (BNIP5), etc.) and downregulated the expression of genes related to mitochondrial biogenesis (ND1, ND2, COX3, ATP6, etc.). Further KEGG pathway enrichment analysis showed that CDCA significantly enriched the signaling pathways of DNA replication, cell cycle, and p53. Collectively, this study demonstrated that CDCA could promote IPEC-J2 proliferation by regulating cell cycle progression and mitochondrial function. These findings provide a new strategy for promoting the intestinal health of pigs by regulating intestinal BA metabolism.

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