MiR-132 down-regulates high glucose-induced β-dystroglycan degradation through Matrix Metalloproteinases-9 up-regulation in primary neurons.
MiR-132 down-regulates high glucose-induced β-dystroglycan degradation through Matrix Metalloproteinases-9 up-regulation in primary neurons.
复制标题
MiR-132 通过上调原代神经元中基质金属蛋白酶 9 下调高葡萄糖诱导的 β-肌营养不良聚糖降解
DOI：
10.1111/jcmm.16669
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发表时间：
2021-08
影响因子：
5.3
通讯作者：
Liu X
中科院分区：
文献类型：
--
作者：
Dou Y;Tan Y;Yu T;Ma X;Zhou Y;Zhao Y;Zhao Y;Liu X
认知功能障碍是糖尿病的并发症之一。遗憾的是，目前还没有有效的方法来阻止其进展。其病理生理机制之一是糖代谢紊乱导致突触蛋白损伤和神经元信号中断。营养不良蛋白位于神经元突触后膜上，连接细胞内细胞骨架和细胞外基质。营养不良蛋白的异常表达影响神经元的生物学功能，导致认知功能障碍。但目前尚无相关研究观察高糖暴露下糖尿病大鼠脑内及原代神经元中β-DystroGan蛋白的变化。我们的数据证实了糖尿病大鼠认知能力的改变；糖尿病大鼠大脑中的海马区和皮质组织中出现了β-DystroGan蛋白降解。我们进一步探索了这一现象背后的机制。当神经元长期暴露在高糖环境中时，microRNA-132(miR-132)在神经元中表达下调。作为miR-132靶点的基质金属蛋白酶-9(MMP9)基因表达上调，MMP9蛋白的高表达和重叠活性可促进β-DG蛋白的降解。在这种情况下，β-DG的降解可能会影响突触之间的结构和功能，这与认知能力下降有关。为阐明糖尿病认知功能障碍的分子机制提供一定的理论依据。
Cognitive dysfunction is one of the complications of diabetes. Unfortunately, there is no effective methods to block its progression currently. One of the pathophysiological mechanisms is synaptic protein damage and neuronal signal disruption because of glucose metabolism disorder. Dystroglycan protein, located in the post‐synaptic membrane of neurons, links the intracellular cytoskeleton with extracellular matrix. Abnormal expression of dystroglycan protein affects neuronal biological functions and leads to cognitive impairment. However, there are no relevant studies to observe the changes of β‐dystroglycan protein in diabetes rat brain and in primary neurons under high glucose exposure. Our data demonstrated the alterations of cognitive abilities in the diabetic rats; β‐dystroglycan protein degradation occurred in hippocampal and cortical tissues in diabetic rat brain. We further explored the mechanisms underlying of this phenomenon. When neurons are exposed to high glucose environment in long‐term period, microRNA‐132 (miR‐132) would be down‐regulated in neurons. Matrix Metalloproteinases‐9 (MMP‐9) mRNA, as a target of miR‐132, could be up‐regulated; higher expression and overlay activity of MMP‐9 protein could increase β‐DG protein degradation. In this way, β‐DG degradation may affect structure and functions among the synapses, which related to cognition decline. It may provide some theoretical basis for elucidating the molecular mechanism of diabetes‐induced cognitive dysfunction.
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DOI：
10.1073/pnas.1015691107
发表时间：
2010-11-23
影响因子：
11.1
作者：
Magill, Stephen T.;Cambronne, Xiaolu A.;Goodman, Richard H.
通讯作者：
Goodman, Richard H.
影响因子：
5.1
作者：
Jasińska M;Miłek J;Cymerman IA;Łęski S;Kaczmarek L;Dziembowska M
通讯作者：
Dziembowska M
影响因子：
16.2
作者：
Holt CE;Schuman EM
通讯作者：
Schuman EM
影响因子：
1.2
作者：
Lu, Zhongming;Piechowicz, Mariel;Qiu, Shenfeng
通讯作者：
Qiu, Shenfeng
影响因子：
4.3
作者：
Deckardt, K.;Weber, I.;van Ravenzwaay, B.
通讯作者：
van Ravenzwaay, B.