Tetramethylpyrazine induces the release of BDNF from BM-MSCs through activation of the PI3K/AKT/CREB pathway
Tetramethylpyrazine induces the release of BDNF from BM-MSCs through activation of the PI3K/AKT/CREB pathway
复制标题
Tetramethylpyrazine 通过激活 PI3K/AKT/CREB 通路诱导 BM-MSC 释放 BDNF
DOI：
10.1002/cbin.11687
复制
发表时间：
2021-08-23
影响因子：
3.9
通讯作者：
Yang, Hao
中科院分区：
文献类型：
--
作者：
Chen, Bo;An, Jing;Yang, Hao
令人信服的证据表明，骨髓间充质干细胞（BM-MSCs）移植可有效治疗中枢神经系统（CNS）损伤和神经退行性疾病。脑间充质干细胞的治疗作用主要归因于其向神经元样细胞的分化，取代损伤和退行性神经元。重要的是，脑基质间充质干细胞释放的神经营养因子还可以拯救损伤和退行性神经元，这在促进神经再生和神经功能恢复方面发挥着生物学上的关键作用。川芎的主要生物活性成分川芎嗪（Tetramethylpyrazine， TMP）有促进脑-间充质干细胞神经元分化的作用。本研究旨在探讨TMP是否调节脑间充质干细胞中神经营养因子的释放。我们研究了TMP对脑-间充质干细胞释放的脑源性神经营养因子（BDNF）的影响，并阐明了其潜在的分子机制。我们的研究结果表明，浓度低于200 μ M的TMP增加了BDNF的释放，并呈剂量依赖性。此外，TMP通过抑制磷脂酰肌醇-4,5-二磷酸3激酶(PI3K)/蛋白激酶B (AKT)/ camp反应元件结合蛋白（CREB）通路，阻断了BDNF从BM-MSCs释放的作用。因此，我们认为TMP可以通过激活PI3K/AKT/CREB通路诱导BDNF从BM-MSCs中释放，从而形成神经保护和前神经源性微环境。这些研究结果表明，TMP具有通过改善脑间充质干细胞的神经营养能力来促进神经保护和神经发生的新治疗潜力，这为通过TMP处理的脑间充质干细胞移植治疗中枢神经系统损伤和神经退行性疾病提供了一种有希望的营养预防和治疗策略。
Compelling evidences suggest that transplantation of bone marrow-derived mesenchymal stem cells (BM-MSCs) can be therapeutically effective for central nervous system (CNS) injuries and neurodegenerative diseases. The therapeutic effect of BM-MSCs mainly attributes to their differentiation into neuron-like cells which replace injured and degenerative neurons. Importantly, the neurotrophic factors released from BM-MSCs can also rescue injured and degenerative neurons, which plays a biologically pivotal role in enhancing neuroregeneration and neurological functional recovery. Tetramethylpyrazine (TMP), the main bioactive ingredient extracted from the traditional Chinese medicinal herb Chuanxiong, has been reported to promote the neuronal differentiation of BM-MSCs. This study aimed to investigate whether TMP regulates the release of neurotrophic factors from BM-MSCs. We examined the effect of TMP on brain-derived neurotrophic factor (BDNF) released from BM-MSCs and elucidated the underlying molecular mechanism. Our results demonstrated that TMP at concentrations of lower than 200 mu M increased the release of BDNF in a dose-dependent manner. Furthermore, the effect of TMP on increasing the release of BDNF from BM-MSCs was blocked by inhibiting the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/protein kinase B (AKT)/cAMP-response element binding protein (CREB) pathway. Therefore, we concluded that TMP could induce the release of BDNF from BM-MSCs through activation of the PI3K/AKT/CREB pathway, leading to the formation of neuroprotective and proneurogenic microenvironment. These findings suggest that TMP possesses novel therapeutic potential to promote neuroprotection and neurogenesis through improving the neurotrophic ability of BM-MSCs, which provides a promising nutritional prevention and treatment strategy for CNS injuries and neurodegenerative diseases via the transplantation of TMP-treated BM-MSCs.