染色体免疫沉淀法探寻小鼠脑缺血后Smad3信号蛋白与Lcn2的结合位点
孔丽萍 （ 徐州矿务集团总医院（徐州医科大学附属第二医院） ）
曹晓伟 （ 徐州矿务集团总医院（徐州医科大学附属第二医院） ）
娄世莹 （ 徐州矿务集团总医院（徐州医科大学附属第二医院） ）
张清秀 （ 南京鼓楼医院 ）
https://doi.org/10.37155/2661-4766-0305-13Abstract
目的：在典型的Smad2/ 3通路中，明确小鼠脑缺血后Smad3信号蛋白与Lcn2基因结合的位点，为研究星形胶质细胞介导的神经炎症反应提供重要依据和视角。为进一步明确转化生长因子-β1(transforming growth factor-β1, TGF-β1)抑制Lcn2表达的分子靶点，提供理论依据。方法：应用染色体免疫沉淀（Chromatin immunoprecipitation，ChIP）的方法，探寻小鼠脑缺血后Smad3信号蛋白与Lcn2基因的结合位点。结果：Smad3信号蛋白与Lcn2基因最可能的结合位点位于Lcn2基因的启动子区chr2:32384637-32385272位置。结论：这一结果初步表明了，Smad3信号蛋白与Lcn2的结合关系及结合位点位置，二者的结合共同促进星形胶质细胞肥大、胶质纤维酸性蛋白（Glial fibrillary acidic protein，GFAP）表达及迁移，明确了神经炎症型星形胶质细胞与LCN2分泌的关系。
Keywords
CHIP;脑缺血;Smad 蛋白;Lcn2基因Full Text
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[6]Suk K. Lipocalin-2 as a therapeutic target for brain injury: An astrocentric perspective[J]. Prog Neurobiol, 2016, 144:158-72.
[7]Kang SS, Ren Y, Liu CC, Kurti A, Baker KE, Bu G, et al. Lipocalin-2 protects the brain during inflammatory conditions[J]. Mol Psychiatry, 2018, 23(2):344-50.
[8]Zamanian JL, Xu L, Foo LC, Nouri N, Zhou L, Giffard RG, et al. Genomic analysis of reactive astrogliosis[J]. J Neurosci, 2012, 32(18):6391-410.
[9]Zhao N, Xu X, Jiang Y, Gao J, Wang F, Xu X, et al. Lipocalin-2 may produce damaging effect after cerebral ischemia by inducing astrocytes classical activation[J]. J Neuroinflammation, 2019, 16(1):168.
[10]Lee S, Park JY, Lee WH, Kim H, Park HC, Mori K, et al. Lipocalin-2 is an autocrine mediator of reactive astrocytosis[J]. J Neurosci, 2009, 29(1):234-49.
[11]Yu Z, Yu P, Chen H, Geller HM. Targeted inhibition of KCa3.1 attenuates TGF-beta-induced reactive astrogliosis through the Smad2/3 signaling pathway[J]. J Neurochem, 2014, 130(1):41-9.
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[14]Wang C, Chen L, Wang L, Wu J. Crystal structure of the MH2 domain of Drosophila[J]. Mad. Sci China C Life Sci, 2009, 52(6):539-44.
[15]Wang G, Weng YC, Han X, Whaley JD, McCrae KR, Chou WH. Lipocalin-2 released in response to cerebral ischaemia mediates reperfusion injury in mice[J]. J Cell Mol Med, 2015, 19(7):1637-45.
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[17]Cregg JM, DePaul MA, Filous AR, Lang BT, Tran A, Silver J. Functional regeneration beyond the glial scar[J]. Exp Neurol, 2014, 253:197-207.
[18]Kim JH, Ko PW, Lee HW, Jeong JY, Lee MG, Kim JH, et al. Astrocyte-derived lipocalin-2 mediates hippocampal damage and cognitive deficits in experimental models of vascular dementia[J]. Glia, 2017, 65(9):1471-90.
Copyright © 2022 孔丽萍,曹晓伟,娄世莹,张清秀
Publishing time:2021-10-31
This work is licensed under a Creative Commons Attribution 4.0 International License
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