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BMP6 通过 Smad2/3 和细胞周期蛋白 D1 通路以及 DACH1 和 TFAP2A 的激活调节人支持细胞的增殖和凋亡。

BMP6 Regulates Proliferation and Apoptosis of Human Sertoli Cells Via Smad2/3 and Cyclin D1 Pathway and DACH1 and TFAP2A Activation.

机构信息

State Key Laboratory of Oncogenes and Related Genes, Renji- Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.

Department of Andrology, Urologic Medical Center, Shanghai General Hospital, Shanghai Jiao Tong University, 100 Haining Road, Shanghai 200080, China.

出版信息

Sci Rep. 2017 Apr 7;7:45298. doi: 10.1038/srep45298.

DOI:10.1038/srep45298
PMID:28387750
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5384448/
Abstract

Sertoli cells are essential for regulating normal spermatogenesis. However, the mechanisms underlying human Sertoli cell development remain largely elusive. Here we examined the function and signaling pathways of BMP6 in regulating human Sertoli cells. RT-PCR, immunocytochemistry and Western blots revealed that BMP6 and its multiple receptors were expressed in human Sertoli cells. CCK-8 and EDU assays showed that BMP6 promoted the proliferation of Sertoli cells. Conversely, BMP6 siRNAs inhibited the division of these cells. Annexin V/PI assay indicated that BMP6 reduced the apoptosis in human Sertoli cells, whereas BMP6 knockdown assumed reverse effects. BMP6 enhanced the expression levels of ZO1, SCF, GDNF and AR in human Sertoli cells, and ELISA assay showed an increase of SCF by BMP6 and a reduction by BMP6 siRNAs. Notably, Smad2/3 phosphorylation and cyclin D1 were enhanced by BMP6 and decreased by BMP6 siRNAs in human Sertoli cells. The levels of DACH1 and TFAP2A were increased by BMP6 and reduced by BMP6 siRNAs, and the growth of human Sertoli cells was inhibited by these siRNAs. Collectively, these results suggest that BMP6 regulates the proliferation and apoptosis of human Sertoli cells via activating the Smad2/3/cyclin D1 and DACH1 and TFAP2A pathway.

摘要

支持细胞对于调节正常精子发生至关重要。然而，人类支持细胞发育的机制在很大程度上仍未被揭示。在这里，我们研究了 BMP6 在调节人类支持细胞中的功能和信号通路。RT-PCR、免疫细胞化学和 Western blot 显示 BMP6 及其多种受体在人类支持细胞中表达。CCK-8 和 EDU 测定表明 BMP6 促进支持细胞的增殖。相反，BMP6 siRNAs 抑制这些细胞的分裂。Annexin V/PI 测定表明 BMP6 减少了人支持细胞的凋亡，而 BMP6 敲低则产生相反的效果。BMP6 增强了人支持细胞中 ZO1、SCF、GDNF 和 AR 的表达水平，ELISA 测定显示 BMP6 增加了 SCF 的表达，而 BMP6 siRNAs 则减少了 SCF 的表达。值得注意的是，BMP6 增强了人支持细胞中 Smad2/3 的磷酸化和 cyclin D1 的表达，而 BMP6 siRNAs 则降低了它们的表达。DACH1 和 TFAP2A 的水平被 BMP6 上调，被 BMP6 siRNAs 下调，这些 siRNAs 抑制了人支持细胞的生长。总之，这些结果表明 BMP6 通过激活 Smad2/3/cyclin D1 和 DACH1 和 TFAP2A 通路来调节人支持细胞的增殖和凋亡。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74d5/5384448/893bc292bd71/srep45298-f7.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74d5/5384448/7c9b4dcd3771/srep45298-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74d5/5384448/893bc292bd71/srep45298-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74d5/5384448/e6c9022f4341/srep45298-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74d5/5384448/ca9a53f9e417/srep45298-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74d5/5384448/82a81f9dd9b7/srep45298-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74d5/5384448/8cec7b78a6dd/srep45298-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74d5/5384448/42de491c5bf1/srep45298-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74d5/5384448/7c9b4dcd3771/srep45298-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74d5/5384448/893bc292bd71/srep45298-f7.jpg

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本文引用的文献

1
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PLoS Genet. 2017 Jan 3;13(1):e1006520. doi: 10.1371/journal.pgen.1006520. eCollection 2017 Jan.
2
Absence of genomic hypomethylation or regulation of cytosine-modifying enzymes with aging in male and female mice.雄性和雌性小鼠随着年龄增长不存在基因组低甲基化或胞嘧啶修饰酶的调控。
Epigenetics Chromatin. 2016 Jul 13;9:30. doi: 10.1186/s13072-016-0080-6. eCollection 2016.
3
Establishment and applications of male germ cell and Sertoli cell lines.
RIG-I and MDA5 are modulated by bone morphogenetic protein (BMP6) and are essential for restricting Zika virus infection in human Sertoli cells.视黄酸诱导基因I（RIG-I）和黑色素瘤分化相关基因5（MDA5）受骨形态发生蛋白（BMP6）调节，对限制寨卡病毒在人睾丸支持细胞中的感染至关重要。
Front Microbiol. 2023 Jan 12;13:1062499. doi: 10.3389/fmicb.2022.1062499. eCollection 2022.
4
The regulatory role of BMP4 in testicular Sertoli cells of Tibetan sheep.BMP4在藏绵羊睾丸支持细胞中的调控作用。
J Anim Sci. 2023 Jan 3;101. doi: 10.1093/jas/skac393.
5
Probing the Potential Mechanism of Quercetin and Kaempferol against Heat Stress-Induced Sertoli Cell Injury: Through Integrating Network Pharmacology and Experimental Validation.探讨槲皮素和山奈酚对抗热应激诱导的支持细胞损伤的潜在机制：通过整合网络药理学和实验验证。
Int J Mol Sci. 2022 Sep 22;23(19):11163. doi: 10.3390/ijms231911163.
6
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Aging (Albany NY). 2020 Nov 24;12(24):25528-25546. doi: 10.18632/aging.104158.
10
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BMC Genomics. 2020 Jan 30;21(1):99. doi: 10.1186/s12864-020-6513-4.
雄性生殖细胞和支持细胞系的建立与应用。
Reproduction. 2016 Aug;152(2):R31-40. doi: 10.1530/REP-15-0546. Epub 2016 Apr 11.
4
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5
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Cell Commun Signal. 2015 Mar 25;13:20. doi: 10.1186/s12964-015-0101-2.
6
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Sci Rep. 2015 Jan 30;5:8084. doi: 10.1038/srep08084.
7
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Spermatogenesis. 2014 Mar 31;4:e28218. doi: 10.4161/spmg.28218. eCollection 2014.
8
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J Cell Mol Med. 2014 Dec;18(12):2499-511. doi: 10.1111/jcmm.12325. Epub 2014 Jun 9.
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Drug Metab Dispos. 2014 Apr;42(4):529-36. doi: 10.1124/dmd.113.054718. Epub 2014 Jan 23.
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