Lipin1 Is Involved in the Pathogenesis of Diabetic Encephalopathy through the PKD/Limk/Cofilin Signaling Pathway.
Lipin1 Is Involved in the Pathogenesis of Diabetic Encephalopathy through the PKD/Limk/Cofilin Signaling Pathway.
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Lipin1 通过 PKD/Limk/Cofilin 信号通路参与糖尿病脑病的发病机制
DOI：
10.1155/2020/1723423
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发表时间：
2020
影响因子：
--
通讯作者：
Chen S
中科院分区：
文献类型：
--
作者：
Xie M;Wang M;Liu W;Xu M;Shang P;Jiang D;Ju L;Wu F;Sun A;Yu S;Zhuang X;Chen S
糖尿病脑病是由糖尿病引起的以认知功能障碍为主要表现的中枢性糖尿病神经病变。然而，其潜在的发病机制和有效的治疗策略仍不清楚。在本研究中，我们研究了Lipin 1，一种磷脂酸磷酸酶，在糖尿病脑病发病机制中的作用。我们发现，在体外，Lipin 1发挥保护作用，高葡萄糖诱导的PC 12细胞活力的减少，而在体内，Lipin 1下调内CA 1海马区在I型糖尿病大鼠模型。CA 1区域内Lipin 1水平的增加伴随着保护作用，包括改善树枝状棘和突触缺陷、突触可塑性相关蛋白、LIM激酶1（p-limk 1）和cofilin的磷酸化，以及增加合成二酰基甘油（DAG）和磷酸化蛋白激酶D（p-PKD）的表达。这些作用与认知障碍的拯救有关，如该糖尿病大鼠模型所示。相反，在CA 1区域内Lipin 1的敲低增强了大鼠的神经元异常和认知障碍的发生。这些结果表明，Lipin 1可能发挥神经保护作用，涉及PKD/Limk/Cofilin信号通路，并可能作为糖尿病脑病的潜在治疗靶点。
Diabetic encephalopathy is a type of central diabetic neuropathy resulting from diabetes mainly manifested as cognitive impairments. However, its underlying pathogenesis and effective treatment strategies remain unclear. In the present study, we investigated the effect of Lipin1, a phosphatidic acid phosphatase enzyme, on the pathogenesis of diabetic encephalopathy. We found that in vitro, Lipin1 exerts protective effects on high glucose-induced reductions of PC12 cell viability, while in vivo, Lipin1 is downregulated within the CA1 hippocampal region in a type I diabetes rat model. Increased levels of Lipin1 within the CA1 region are accompanied with protective effects including amelioration of dendritic spine and synaptic deficiencies, phosphorylation of the synaptic plasticity-related proteins, LIM kinase 1 (p-limk1) and cofilin, as well as increases in the synthesis of diacylglycerol (DAG), and the expression of phosphorylated protein kinase D (p-PKD). These effects are associated with the rescue of cognitive disorders as shown in this rat model of diabetes. In contrast, knockdown of Lipin1 within the CA1 region enhanced neuronal abnormalities and the genesis of cognitive impairment in rats. These results suggest that Lipin1 may exert neuroprotective effects involving the PKD/Limk/Cofilin signaling pathway and may serve as a potential therapeutic target for diabetic encephalopathy.
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影响因子：
21.3
作者：
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通讯作者：
Storz P
影响因子：
2.7
作者：
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DELACOUR, J
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5
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10.5
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影响因子：
11.4
作者：
Loeffler, Mona C.;Mayer, Alexander E.;Sumara, Grzegorz
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