Interference with lactate metabolism by mmu-miR-320-3p via negatively regulating GLUT3 signaling in mouse Sertoli cells.
Interference with lactate metabolism by mmu-miR-320-3p via negatively regulating GLUT3 signaling in mouse Sertoli cells.
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mmu-miR-320-3p 通过负向调节小鼠支持细胞中的 GLUT3 信号传导来干扰乳酸代谢。
DOI：
10.1038/s41419-018-0958-2
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发表时间：
2018-09-20
影响因子：
9
通讯作者：
Li W
中科院分区：
文献类型：
--
作者：
Zhang LL;Ma J;Yang B;Zhao J;Yan BY;Zhang YQ;Li W
支持细胞（SC）的保育功能的破坏，通过减少乳酸的产生，一个优选的能源基板的生殖细胞（精母细胞和精子细胞），是与生精功能障碍，如SC-唯一综合征（SCOS）密切相关。然而，这一复杂的发病机制是否受到某些miRNAs在转录后水平的调控仍然令人着迷，但在很大程度上是未知的。在这里，我们首次表明mmu-miR-320- 3 p仅在小鼠SC中表达，并且这种表达在白消安处理的小鼠睾丸中被显著诱导。最有效的刺激生殖细胞类型的诱导睾丸发育诱导mmu-miR-320- 3 p的表达是减数分裂的精母细胞和单倍体精子细胞。在功能上，外源mmu-miR-320- 3 p在SC中的强制表达通过引起少精子症和精子活动性缺陷而损害男性生育力。在机制上，mmu-miR-320- 3 p通过直接抑制葡萄糖转运蛋白3（GLUT 3）表达来负调节SC的乳酸产生。因此，mmu-miR-320- 3 p/GLUT 3级联反应的失调以及由此导致的乳酸缺乏可能是促成SC功能障碍导致的生殖细胞损失的关键分子事件。对这种重要的循环miRNA的持续奋进可能会为SC保育功能的表观遗传调控和无精子症的病因学提供新的见解，并为SCOS提供新的治疗和预后靶点。
Disruption of the nursery function in Sertoli cells (SCs) by reducing lactate production, a preferred energy substrate for developed germ cells (spermatocytes and spermatids), is tightly associated with spermatogenic failure such as SC-only syndrome (SCOS). However, whether this complicated pathogenesis is regulated by certain miRNAs at the post-transcriptional level remain fascinating but largely unknown. Here we show for the first time that mmu-miR-320-3p was exclusively expressed in murine SCs and this expression was significantly induced in busulphan-treated murine testis. The most efficient stimulatory germ cell types for the induction of apoptosis-elicited mmu-miR-320-3p expression were meiotic spermatocytes and haploid spermatids. Functionally, forced expression of the exogenous mmu-miR-320-3p in SCs compromises male fertility by causing oligozoospermia and defection of sperm mobility. Mechanistically, mmu-miR-320-3p negatively regulates lactate production of SCs by directly inhibiting glucose transporter 3 (GLUT3) expression. Thus, dysregulation of mmu-miR-320-3p/GLUT3 cascade and consequently of lactate deficiency may be a key molecular event contributing the germ cell loss by SC dysfunction. Future endeavor in the continuous investigation of this important circulating miRNA may shed novel insights into epigenetic regulation of SCs nursery function and the etiology of azoospermia, and offers novel therapeutic and prognostic targets for SCOS.
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癌细胞对葡萄糖限制和双胍类药物敏感性的代谢决定因素。
影响因子：
64.8
作者：
Birsoy, Kivanc;Possemato, Richard;Lorbeer, Franziska K.;Bayraktar, Erol C.;Thiru, Prathapan;Yucel, Burcu;Wang, Tim;Chen, Walter W.;Clish, Clary B.;Sabatini, David M.
通讯作者：
Sabatini, David M.
影响因子：
3.7
作者：
Li W;Zhu S;Li J;Huang Y;Zhou R;Fan X;Yang H;Gong X;Eissa NT;Jahnen-Dechent W;Wang P;Tracey KJ;Sama AE;Wang H
通讯作者：
Wang H
影响因子：
7.5
作者：
Babapoor, Sankhiros;Horwich, Michael;Dadras, Soheil S.
通讯作者：
Dadras, Soheil S.
影响因子：
3.6
作者：
Ding, Jin;Wang, Hui;Li, Wei
通讯作者：
Li, Wei
影响因子：
5.8
作者：
Nair, Neena
通讯作者：
Nair, Neena