CDKN1C (P57): one of the determinants of human endometrial stromal cell decidualization.[Epub ahead of print](SCI收录,影响因子3.4)
CDKN1C (P57): one of the determinants of human endometrial stromal cell decidualization.[Epub ahead of print](SCI收录,影响因子3.4)
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DOI：
10.1093/biolre/iox187
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发表时间：
2018
期刊：
影响因子：
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通讯作者：
通讯作者）
中科院分区：
文献类型：
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作者：
Lan Wang;Hui Yang;Linli Hu;Dan Hu;Hanwang Zhang;Kun Qian（钱坤;通讯作者）
去个体化是由黄体酮和cAMP通路的串扰调控的。它涉及基因表达的广泛重编程，包括广泛的功能。为了研究细胞周期调控基因如何驱动人子宫内膜基质细胞（ESC）退出细胞周期并进入分化，我们采用8-Br-cAMP和MPA处理原代培养的ESC，并通过流式细胞术观察细胞周期分布。利用微阵列技术研究了高通量细胞周期调控基因的表达。为了验证微阵列芯片的结果，我们采用免疫组织化学和光密度半定量方法分析子宫内膜（n = 6）和妊娠早期蜕膜（n = 6）增殖期细胞周期调节蛋白的表达。此外，我们选择了细胞周期蛋白依赖性激酶抑制剂1c （CDKN1C，也称为P57）和细胞周期蛋白依赖性激酶抑制剂2b (CDKN2B，也称为P15)，通过RNAi方法研究它们在去个性化过程中的作用。ESC在去个体化过程中在G0/G1检查点被捕。细胞周期调控基因esp57和p15在体外和体内均上调，而细胞周期蛋白D1 （CCND1）、细胞周期蛋白依赖性激酶2 （CDK2）和细胞分裂周期蛋白2同源物（CDC2）在体外和体内均下调。P57siRNA损伤ESC脱体细胞，引起不同的形态学和超微结构改变，泌乳素分泌相对减少，而p15sirna无影响。我们得出结论，p15、CCND1、CDK2和cdc2在体外和体内均可能参与ESC退出细胞周期并进入分化。由于p57对细胞周期分布的影响，它是ESC分化的关键决定因素之一，但它与蜕膜特异性转录因子的关联需要进一步研究。
Decidualization is regulated by crosstalk of progesterone and the cAMP pathway. It involves extensive reprogramming of gene expression and includes a wide range of functions. To investigate how cell cycle regulatory genes drive the human endometrial stromal cell (ESC) exit cell cycle and enter differentiation, primary cultured ESC was treated with 8-Br-cAMP and MPA and cell cycle distribution was investigated by flow cytometry. High-throughput cell cycle regulatory gene expression was also studied by microarray. To validate the results of microarray chip, immunohistochemistry and semi-quantitative method of optical density were used to analyze the expression of cell cycle regulator proteins in proliferative phase of endometrium (n = 6) and early pregnancy decidua (n = 6). In addition, we selected cyclin-dependent kinase inhibitor 1c (CDKN1C, also known as P57) and cyclin-dependent kinase inhibitor 2b (CDKN2B, also known as P15) in order to study their role in the process of decidualization by the RNAi method. ESC was arrested at G0/G1 checkpoints during decidualization. Cell cycle regulatory genesP57andP15were upregulated, while cyclin D1 (CCND1), cyclin-dependent kinase 2 (CDK2), and cell division cycle protein 2 homolog (CDC2) were downregulated during ESC differentiation both in vitro and vivo.P57siRNA impaired ESC decidualization and caused different morphological and ultrastructural changes as well as a relatively low secretion of prolactin, butP15siRNA had no effects. We concluded thatP15, CCND1, CDK2, andCDC2may participate in ESC withdraw from the cell cycle and go into differentiation both in vitro and in vivo.P57is one of the key determinants of ESC differentiation due to its effect on the cell cycle distribution, but its association with the decidua-specific transcription factor needs further investigation.