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补肾中药通过ERK/MAPK通路诱导SOCS-3表达并促进人早孕滋养层细胞生长。

Kidney-Replenishing Herb Induces SOCS-3 Expression via ERK/MAPK Pathway and Improves Growth of the First-Trimester Human Trophoblast Cells.

作者信息

Xing Chang-Ying, Zhang De-Xiang, Gui Sui-Qi, Tao Min-Fang

机构信息

Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.

Affiliated Hospital of Nantong University, Nantong 226001, China.

出版信息

Evid Based Complement Alternat Med. 2017;2017:2473431. doi: 10.1155/2017/2473431. Epub 2017 Sep 28.

DOI:10.1155/2017/2473431
PMID:29234375
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5637846/
Abstract

Kidney-replenishing herb is a traditional medicine formula in China which has been widely used for clinical treatment of recurrent miscarriage. Our previous study showed that Kidney-replenishing herb could promote proliferation and inhibit apoptosis of the human first-trimester trophoblasts. In the present study, we further explored the potential mechanism and signal pathway of Kidney-replenishing herb on human trophoblast cells. Our research showed that Kidney-replenishing herb stimulated proliferation and reduced apoptosis of human trophoblast cells in vitro, and this appeared to be positive correlation with SOCS-3 transcription, suggesting that Kidney-replenishing herb regulated biological functions of human trophoblast cells by inducing SCOS-3 expression. Furthermore, the Kidney-replenishing herb treatment stimulated the phosphorylation of ERK1/2, and blocking the signaling pathway by mitogen-activated protein MAPK (MEK) inhibitor, U0126, inhibited Kidney-replenishing herb-induced SOCS-3 transcription, depressed proliferation, and promoted apoptosis of human trophoblasts. Kidney-replenishing herbs still induced ERK1/2 phosphorylation after SOCS-3 siRNA silence. Overexpression of SOCS-3 stimulated the proliferation of trophoblast. These findings suggest that SOCS-3 expression is induced by Kidney-replenishing herbs via activation of MAPK pathways, and this may possibly be involved in promoting human trophoblast cells growth which is contributed to embryo development.

摘要

补肾中药是中国的一种传统中药配方，已被广泛用于复发性流产的临床治疗。我们之前的研究表明，补肾中药可以促进人早孕滋养层细胞的增殖并抑制其凋亡。在本研究中，我们进一步探讨了补肾中药对人滋养层细胞作用的潜在机制和信号通路。我们的研究表明，补肾中药在体外可刺激人滋养层细胞的增殖并减少其凋亡，这似乎与SOCS-3转录呈正相关，提示补肾中药通过诱导SCOS-3表达来调节人滋养层细胞的生物学功能。此外，补肾中药处理可刺激ERK1/2的磷酸化，用丝裂原活化蛋白激酶（MAPK）抑制剂U0126阻断该信号通路，可抑制补肾中药诱导的SOCS-3转录，抑制人滋养层细胞的增殖并促进其凋亡。在SOCS-3 siRNA沉默后，补肾中药仍可诱导ERK1/2磷酸化。SOCS-3的过表达可刺激滋养层细胞的增殖。这些发现提示，补肾中药通过激活MAPK通路诱导SOCS-3表达，这可能参与促进人滋养层细胞生长，从而有助于胚胎发育。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08ec/5637846/a288349a84d3/ECAM2017-2473431.010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08ec/5637846/e3f700264037/ECAM2017-2473431.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08ec/5637846/2ee574bbcc48/ECAM2017-2473431.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08ec/5637846/05fac8d18449/ECAM2017-2473431.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08ec/5637846/0eafd4bd789f/ECAM2017-2473431.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08ec/5637846/ce52617f12df/ECAM2017-2473431.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08ec/5637846/1b0747f9f839/ECAM2017-2473431.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08ec/5637846/605b2914780e/ECAM2017-2473431.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08ec/5637846/9d8ec5a2239f/ECAM2017-2473431.008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08ec/5637846/76c92549d9bd/ECAM2017-2473431.009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08ec/5637846/a288349a84d3/ECAM2017-2473431.010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08ec/5637846/e3f700264037/ECAM2017-2473431.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08ec/5637846/2ee574bbcc48/ECAM2017-2473431.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08ec/5637846/05fac8d18449/ECAM2017-2473431.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08ec/5637846/0eafd4bd789f/ECAM2017-2473431.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08ec/5637846/ce52617f12df/ECAM2017-2473431.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08ec/5637846/1b0747f9f839/ECAM2017-2473431.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08ec/5637846/605b2914780e/ECAM2017-2473431.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08ec/5637846/9d8ec5a2239f/ECAM2017-2473431.008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08ec/5637846/76c92549d9bd/ECAM2017-2473431.009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08ec/5637846/a288349a84d3/ECAM2017-2473431.010.jpg

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Intranuclear crosstalk between extracellular regulated kinase1/2 and signal transducer and activator of transcription 3 regulates JEG-3 choriocarcinoma cell invasion and proliferation.细胞外调节激酶1/2与信号转导及转录激活因子3之间的核内串扰调控JEG-3绒毛膜癌细胞的侵袭与增殖。
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Suppressor of cytokine signalling protein SOCS3 expression is increased at sites of acute and chronic inflammation.抑制细胞因子信号转导蛋白 SOCS3 的表达在急性和慢性炎症部位增加。
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Prostasin regulates human placental trophoblast cell proliferation via the epidermal growth factor receptor signaling pathway.Prostasin 通过表皮生长因子受体信号通路调节人胎盘滋养层细胞增殖。
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Biol Reprod. 2008 Jun;78(6):1102-10. doi: 10.1095/biolreprod.107.063503. Epub 2008 Mar 5.