Human adipose tissue-derived multilineage progenitor cells exposed to oxidative stress induce neurite outgrowth in PC12 cells through p38 MAPK signaling.
Human adipose tissue-derived multilineage progenitor cells exposed to oxidative stress induce neurite outgrowth in PC12 cells through p38 MAPK signaling.
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DOI：
10.1186/1471-2121-13-21
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发表时间：
2012-08-07
期刊：
影响因子：
--
通讯作者：
Hayakawa T
中科院分区：
文献类型：
--
作者：
Moriyama M;Moriyama H;Ueda A;Nishibata Y;Okura H;Ichinose A;Matsuyama A;Hayakawa T
脂肪组织含有多能间充质干细胞群，这些干细胞也分泌各种细胞因子和生长因子来支持受损组织的修复。在这项研究中，我们研究了氧化应激对人类脂肪来源的多谱系祖细胞（hADMPCs）在大鼠嗜铬细胞瘤细胞系（PC12）神经突生长中的作用。我们发现，丁硫氨酸亚砜（BSO）处理引起的hADMPCs谷胱甘肽缺失，通过上调hADMPCs中骨形态发生蛋白2 （BMP2）和成纤维细胞生长因子2 （FGF2）的转录和分泌，促进PC12细胞的神经突生长。添加n -乙酰半胱氨酸（细胞内抗氧化剂谷胱甘肽的前体）可以抑制bso介导的BMP2和FGF2的上调。此外，BSO处理引起hampcs中p38 MAPK的磷酸化。抑制p38 MAPK足以抑制BMP2和FGF2的表达，而这种表达通过p38 MAPK的上游分子MKK6的组成活性形式的过表达而显著上调。我们的研究结果清楚地表明，谷胱甘肽的消耗，以及活性氧的积累，刺激了p38 MAPK的激活，以及随后在hADMPCs中BMP2和FGF2的表达。因此，将hADMPCs移植到中风和帕金森病等神经退行性病变中，其中移植的hADMPCs暴露于氧化应激，可以成为简单安全治疗的基础。
Adipose tissues contain populations of pluripotent mesenchymal stem cells that also secrete various cytokines and growth factors to support repair of damaged tissues. In this study, we examined the role of oxidative stress on human adipose-derived multilineage progenitor cells (hADMPCs) in neurite outgrowth in cells of the rat pheochromocytoma cell line (PC12). We found that glutathione depletion in hADMPCs, caused by treatment with buthionine sulfoximine (BSO), resulted in the promotion of neurite outgrowth in PC12 cells through upregulation of bone morphogenetic protein 2 (BMP2) and fibroblast growth factor 2 (FGF2) transcription in, and secretion from, hADMPCs. Addition of N-acetylcysteine, a precursor of the intracellular antioxidant glutathione, suppressed the BSO-mediated upregulation of BMP2 and FGF2. Moreover, BSO treatment caused phosphorylation of p38 MAPK in hADMPCs. Inhibition of p38 MAPK was sufficient to suppress BMP2 and FGF2 expression, while this expression was significantly upregulated by overexpression of a constitutively active form of MKK6, which is an upstream molecule from p38 MAPK. Our results clearly suggest that glutathione depletion, followed by accumulation of reactive oxygen species, stimulates the activation of p38 MAPK and subsequent expression of BMP2 and FGF2 in hADMPCs. Thus, transplantation of hADMPCs into neurodegenerative lesions such as stroke and Parkinson’s disease, in which the transplanted hADMPCs are exposed to oxidative stress, can be the basis for simple and safe therapies.
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脂肪来源的间充质干细胞通过 PI3-K/Akt 激活上调 XIAP，保护 PC12 细胞免受谷氨酸兴奋性毒性诱导的细胞凋亡。
影响因子：
4.5
作者：
Lu, Shan;Lu, Chunhua;Zhao, Robert Chunhua
通讯作者：
Zhao, Robert Chunhua
影响因子：
3
作者：
Okura, Hanayuki;Komoda, Hiroshi;Matsuyama, Akifumi
通讯作者：
Matsuyama, Akifumi
影响因子：
4.5
作者：
Ikegame, Yuka;Yamashita, Kentaro;Iwama, Toru
通讯作者：
Iwama, Toru
DOI：
10.1152/ajpgi.00343.2009
发表时间：
2010-03-01
影响因子：
4.5
作者：
Anitha, Mallappa;Shahnavaz, Nikrad;Srinivasan, Shanthi
通讯作者：
Srinivasan, Shanthi
影响因子：
4.1
作者：
Komoda, Hiroshi;Okura, Hanayuki;Matsuyama, Akifumi
通讯作者：
Matsuyama, Akifumi