周细胞在中枢神经系统中作用的研究进展
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摘要
周细胞(pericyte)是位于血管内皮与基膜间的一种多功能细胞。目前认为周细胞对血管生成、免疫调节及多种组织器官的成熟和稳定均有重要意义。研究证实,周细胞在脑血管病、神经退行性疾病、脑损伤及脑肿瘤等多种神经系统疾病的发生发展中也具有重要作用。本文结合最新研究,对周细胞在中枢神经系统中的作用进行综述,以期为深入探明周细胞的作用机制及发现新的治疗靶向提供线索。
引文
[1]Winkler EA,Bell RD,Zlokovic BV.Central nervous system pericytes in health and disease[J].Nat Neurosci,2011,14(11):1398-1405.DOI:10.1038/nn.2946.
[2]林灵,叶田园,程阳阳,等.从血管神经单元角度探讨薯蓣皂苷元抗血管性痴呆的作用机制[J].时珍国医国药,2017(06):1432-1435.DOI:10.16557/j.cnki.1000-7547.2017.05.010.
[3]Sweeney MD,Ayyadurai S,Zlokovic BV.Pericytes of the neurovascular unit:key functions and signaling pathways[J].Nat Neurosci,2016,19(6):771-783.DOI:10.1038/nn.4288.
[4]ElAli A,Theriault P,Rivest S.The role of pericytes in neurovascular unit remodeling in brain disorders[J].Int J Mol Sci,2014,15(4):6453-6474.DOI:10.3390/ijms15046453.
[5]潘鹏宇.周细胞在蛛网膜下腔出血后血脑屏障损伤的作用及机制研究[D].第三军医大学,2017.DOI:10.3390/ijms15046453.
[6]Kloc M,Kubiak JZ,Li XC,et al.Pericytes,microvasular dysfunction,and chronic rejection[J].Transplantation,2015,99(4):658-667.DOI:10.1097/TP.0000000000000648.
[7]Trost A,Lange S,Schroedl F,et al.Brain and retinal pericytes:origin,function and role[J].Front Cell Neurosci,2016,10:20.DOI:10.3389/fncel.2016.00020.
[8]Rustenhoven J,Smyth LC,Jansson D,et al.Modelling physiological and pathological conditions to study pericyte biology in brain function and dysfunction[J].BMC Neurosci,2018,19(1):6.DOI:10.1186/s12868-018-0405-4.
[9]Damisah EC,Hill RA,Tong L,et al.A fluoro-Nissl dye identifies pericytes as distinct vascular mural cells during in vivo brain imaging[J].Nat Neurosci,2017,20(7):1023-1032.DOI:10.1038/nn.4564.
[10]Birbrair A,Zhang T,Files DC,et al.Type-1 pericytes accumulate after tissue injury and produce collagen in an organ-dependent manner[J].Stem Cell Res Ther,2014,5(6):122.DOI:10.1186/scrt512.
[11]Garbuzova-Davis S,Sanberg PR.Blood-CNS barrier impairment in ALS patients versus an animal model[J].Front Cell Neurosci,2014,8:21.DOI:10.3389/fncel.2014.00021.
[12]Winkler EA,Sengillo JD,Sullivan JS,et al.Blood-spinal cord barrier breakdown and pericyte reductions in amyotrophic lateral sclerosis[J].Acta Neuropathol,2013,125(1):111-120.DOI:10.1007/s00401-012-1039-8.
[13]查雨锋,傅晓钟,张顺,等.大鼠脑微血管内皮细胞与周细胞、星形胶质细胞共培养建立体外血脑屏障模型[J].中国药理学通报,2015(05):730-735.DOI:10.3969/j.issn.1001-1978.2015.05.027.
[14]Underly RG,Levy M,Hartmann DA,et al.Pericytes as inducers of rapid,matrix metalloproteinase-9-dependent capillary damage during ischemia[J].J Neurosci,2017,37(1):129-140.DOI:10.1523/JNEUROSCI.2891-16.2016.
[15]Winkler EA,Sagare AP,Zlokovic BV.The pericyte:a forgotten cell type with important implications for Alzheimer’s disease?[J].Brain Pathol,2014,24(4):371-386.DOI:10.1111/bpa.12152.
[16]Rivera LB,Brekken RA.SPARC promotes pericyte recruitment via inhibition of endoglin-dependent TGF-beta1 activity[J].J Cell Biol,2011,193(7):1305-1319.DOI:10.1083/jcb.201011143.
[17]Chen J,Luo Y,Hui H,et al.CD146 coordinates brain endothelial cell-pericyte communication for blood-brain barrier development[J].Proc Natl Acad Sci USA,2017,114(36):E7622-E7631.DOI:10.1073/pnas.1710848114.
[18]雷万龙,袁群芳,董志宏,等.慢性局灶脑缺血区血管周细胞的形态学观察[J].神经解剖学杂志,2001(04):373-376.DOI:10.3969/j.issn.1000-7547.2001.04.017.
[19]Wang S,Cao C,Chen Z,et al.Pericytes regulate vascular basement membrane remodeling and govern neutrophil extravasation during inflammation[J].PLo S One,2012,7(9):e45499.DOI:10.1371/journal.pone.0045499.
[20]Fernandez-Klett F,Offenhauser N,Dirnagl U,et al.Pericytes in capillaries are contractile in vivo,but arterioles mediate functional hyperemia in the mouse brain[J].Proc Natl Acad Sci USA,2010,107(51):22290-22295.DOI:10.1073/pnas.1011321108.
[21]Rustenhoven J,Smyth LC,Jansson D,et al.Modelling physiological and pathological conditions to study pericyte biology in brain function and dysfunction[J].BMC Neurosci,2018,19(1):6.DOI:10.1186/s12868-018-0405-4.
[22]De La Fuente AG,Lange S,Silva ME,et al.Pericytes stimulate oligodendrocyte progenitor cell differentiation during CNS remyelination[J].Cell Rep,2017,20(8):1755-1764.DOI:10.1016/j.celrep.2017.08.007.
[23]苗莹莹,陈杰,张宾.Notch/JNK信号在低氧致大鼠皮层神经元损伤中的作用研究[J].神经解剖学杂志,2017(05):567-572.DOI:10.16557/j.cnki.1000-7547.2017.05.010.
[24]Arboleda-Velasquez JF,Primo V,Graham M,et al.Notch signaling functions in retinal pericyte survival[J].Invest Ophthalmol Vis Sci,2014,55(8):5191-5199.DOI:10.1167/iovs.14-14046.
[25]Sagare AP,Sweeney MD,Makshanoff J,et al.Shedding of soluble platelet-derived growth factor receptor-beta from human brain pericytes[J].Neurosci Lett,2015,607:97-101.DOI:10.1016/j.neulet.2015.09.025.
[26]Harrell CR,Simovic MB,Fellabaum C,et al.Molecular mechanisms underlying therapeutic potential of pericytess[J].J Biomed Sci,2018,25(1):21.DOI:10.1186/s12929-018-0423-7.
[27]Guimaraes-Camboa N,Cattaneo P,Sun Y,et al.Pericytes of multiple organs do not behave as mesenchymal stem cells in vivo[J].Cell Stem Cell,2017,20(3):345-359.DOI:10.1016/j.stem.2016.12.006.
[28]Kofler NM,Cuervo H,Uh MK,et al.Combined deficiency of Notch1 and Notch3 causes pericyte dysfunction,models CADASIL,and results in arteriovenous malformations[J].Sci Rep,2015,5:16449.DOI:10.1038/srep16449.
[29]Rustenhoven J,Aalderink M,Scotter EL,et al.TGF-beta1 regulates human brain pericyte inflammatory processes involved in neurovasculature function[J].J Neuroinflammation,2016,13:37.DOI:10.1186/s12974-016-0503-0.
[30]Lee S,Elaskandrany M,Lau LF,et al.Interplay between CCN1and Wnt5a in endothelial cells and pericytes determines the angiogenic outcome in a model of ischemic retinopathy[J].Sci Rep,2017,7(1):1405.DOI:10.1038/s41598-017-01585-8.
[31]Li Y,Lucas-Osma AM,Black S,et al.Pericytes impair capillary blood flow and motor function after chronic spinal cord injury[J].Nat Med,2017,23(6):733-741.DOI:10.1038/nm.4331.
[32]Kolinko Y,Kralickova M,Tonar Z.The impact of pericytes on the brain and approaches for their morphological analysis[J].J Chem Neuroanat,2018,91:35-45.DOI:10.1016/j.jchemneu.2018.04.003.
[33]李强,阮怀珍,冯华.周细胞在出血性脑卒中中的作用[J].中华神经医学杂志,2015(10):1070-1073.DOI:10.3760/cma.j.issn.1671-8925.2015.10.022.
[34]Giannoni P,Badaut J,Dargazanli C,et al.The pericyte-glia interface at the blood-brain barrier[J].Clin Sci(Lond),2018,132(3):361-374.DOI:10.1042/CS20171634.
[35]Ozen I,Deierborg T,Miharada K,et al.Brain pericytes acquire a microglial phenotype after stroke[J].Acta Neuropathol,2014,128(3):381-396.DOI:10.1007/s00401-014-1295-x.
[36]Caspani EM,Crossley PH,Redondo-Garcia C,et al.Glioblastoma:a pathogenic crosstalk between tumor cells and pericytes[J].PLo S One,2014,9(7):e101402.DOI:10.1371/journal.pone.0101402.
[37]Ribeiro AL,Okamoto OK.Combined effects of pericytes in the tumor microenvironment[J].Stem Cells Int,2015:868475.DOI:10.1155/2015/868475.
[2]林灵,叶田园,程阳阳,等.从血管神经单元角度探讨薯蓣皂苷元抗血管性痴呆的作用机制[J].时珍国医国药,2017(06):1432-1435.DOI:10.16557/j.cnki.1000-7547.2017.05.010.
[3]Sweeney MD,Ayyadurai S,Zlokovic BV.Pericytes of the neurovascular unit:key functions and signaling pathways[J].Nat Neurosci,2016,19(6):771-783.DOI:10.1038/nn.4288.
[4]ElAli A,Theriault P,Rivest S.The role of pericytes in neurovascular unit remodeling in brain disorders[J].Int J Mol Sci,2014,15(4):6453-6474.DOI:10.3390/ijms15046453.
[5]潘鹏宇.周细胞在蛛网膜下腔出血后血脑屏障损伤的作用及机制研究[D].第三军医大学,2017.DOI:10.3390/ijms15046453.
[6]Kloc M,Kubiak JZ,Li XC,et al.Pericytes,microvasular dysfunction,and chronic rejection[J].Transplantation,2015,99(4):658-667.DOI:10.1097/TP.0000000000000648.
[7]Trost A,Lange S,Schroedl F,et al.Brain and retinal pericytes:origin,function and role[J].Front Cell Neurosci,2016,10:20.DOI:10.3389/fncel.2016.00020.
[8]Rustenhoven J,Smyth LC,Jansson D,et al.Modelling physiological and pathological conditions to study pericyte biology in brain function and dysfunction[J].BMC Neurosci,2018,19(1):6.DOI:10.1186/s12868-018-0405-4.
[9]Damisah EC,Hill RA,Tong L,et al.A fluoro-Nissl dye identifies pericytes as distinct vascular mural cells during in vivo brain imaging[J].Nat Neurosci,2017,20(7):1023-1032.DOI:10.1038/nn.4564.
[10]Birbrair A,Zhang T,Files DC,et al.Type-1 pericytes accumulate after tissue injury and produce collagen in an organ-dependent manner[J].Stem Cell Res Ther,2014,5(6):122.DOI:10.1186/scrt512.
[11]Garbuzova-Davis S,Sanberg PR.Blood-CNS barrier impairment in ALS patients versus an animal model[J].Front Cell Neurosci,2014,8:21.DOI:10.3389/fncel.2014.00021.
[12]Winkler EA,Sengillo JD,Sullivan JS,et al.Blood-spinal cord barrier breakdown and pericyte reductions in amyotrophic lateral sclerosis[J].Acta Neuropathol,2013,125(1):111-120.DOI:10.1007/s00401-012-1039-8.
[13]查雨锋,傅晓钟,张顺,等.大鼠脑微血管内皮细胞与周细胞、星形胶质细胞共培养建立体外血脑屏障模型[J].中国药理学通报,2015(05):730-735.DOI:10.3969/j.issn.1001-1978.2015.05.027.
[14]Underly RG,Levy M,Hartmann DA,et al.Pericytes as inducers of rapid,matrix metalloproteinase-9-dependent capillary damage during ischemia[J].J Neurosci,2017,37(1):129-140.DOI:10.1523/JNEUROSCI.2891-16.2016.
[15]Winkler EA,Sagare AP,Zlokovic BV.The pericyte:a forgotten cell type with important implications for Alzheimer’s disease?[J].Brain Pathol,2014,24(4):371-386.DOI:10.1111/bpa.12152.
[16]Rivera LB,Brekken RA.SPARC promotes pericyte recruitment via inhibition of endoglin-dependent TGF-beta1 activity[J].J Cell Biol,2011,193(7):1305-1319.DOI:10.1083/jcb.201011143.
[17]Chen J,Luo Y,Hui H,et al.CD146 coordinates brain endothelial cell-pericyte communication for blood-brain barrier development[J].Proc Natl Acad Sci USA,2017,114(36):E7622-E7631.DOI:10.1073/pnas.1710848114.
[18]雷万龙,袁群芳,董志宏,等.慢性局灶脑缺血区血管周细胞的形态学观察[J].神经解剖学杂志,2001(04):373-376.DOI:10.3969/j.issn.1000-7547.2001.04.017.
[19]Wang S,Cao C,Chen Z,et al.Pericytes regulate vascular basement membrane remodeling and govern neutrophil extravasation during inflammation[J].PLo S One,2012,7(9):e45499.DOI:10.1371/journal.pone.0045499.
[20]Fernandez-Klett F,Offenhauser N,Dirnagl U,et al.Pericytes in capillaries are contractile in vivo,but arterioles mediate functional hyperemia in the mouse brain[J].Proc Natl Acad Sci USA,2010,107(51):22290-22295.DOI:10.1073/pnas.1011321108.
[21]Rustenhoven J,Smyth LC,Jansson D,et al.Modelling physiological and pathological conditions to study pericyte biology in brain function and dysfunction[J].BMC Neurosci,2018,19(1):6.DOI:10.1186/s12868-018-0405-4.
[22]De La Fuente AG,Lange S,Silva ME,et al.Pericytes stimulate oligodendrocyte progenitor cell differentiation during CNS remyelination[J].Cell Rep,2017,20(8):1755-1764.DOI:10.1016/j.celrep.2017.08.007.
[23]苗莹莹,陈杰,张宾.Notch/JNK信号在低氧致大鼠皮层神经元损伤中的作用研究[J].神经解剖学杂志,2017(05):567-572.DOI:10.16557/j.cnki.1000-7547.2017.05.010.
[24]Arboleda-Velasquez JF,Primo V,Graham M,et al.Notch signaling functions in retinal pericyte survival[J].Invest Ophthalmol Vis Sci,2014,55(8):5191-5199.DOI:10.1167/iovs.14-14046.
[25]Sagare AP,Sweeney MD,Makshanoff J,et al.Shedding of soluble platelet-derived growth factor receptor-beta from human brain pericytes[J].Neurosci Lett,2015,607:97-101.DOI:10.1016/j.neulet.2015.09.025.
[26]Harrell CR,Simovic MB,Fellabaum C,et al.Molecular mechanisms underlying therapeutic potential of pericytess[J].J Biomed Sci,2018,25(1):21.DOI:10.1186/s12929-018-0423-7.
[27]Guimaraes-Camboa N,Cattaneo P,Sun Y,et al.Pericytes of multiple organs do not behave as mesenchymal stem cells in vivo[J].Cell Stem Cell,2017,20(3):345-359.DOI:10.1016/j.stem.2016.12.006.
[28]Kofler NM,Cuervo H,Uh MK,et al.Combined deficiency of Notch1 and Notch3 causes pericyte dysfunction,models CADASIL,and results in arteriovenous malformations[J].Sci Rep,2015,5:16449.DOI:10.1038/srep16449.
[29]Rustenhoven J,Aalderink M,Scotter EL,et al.TGF-beta1 regulates human brain pericyte inflammatory processes involved in neurovasculature function[J].J Neuroinflammation,2016,13:37.DOI:10.1186/s12974-016-0503-0.
[30]Lee S,Elaskandrany M,Lau LF,et al.Interplay between CCN1and Wnt5a in endothelial cells and pericytes determines the angiogenic outcome in a model of ischemic retinopathy[J].Sci Rep,2017,7(1):1405.DOI:10.1038/s41598-017-01585-8.
[31]Li Y,Lucas-Osma AM,Black S,et al.Pericytes impair capillary blood flow and motor function after chronic spinal cord injury[J].Nat Med,2017,23(6):733-741.DOI:10.1038/nm.4331.
[32]Kolinko Y,Kralickova M,Tonar Z.The impact of pericytes on the brain and approaches for their morphological analysis[J].J Chem Neuroanat,2018,91:35-45.DOI:10.1016/j.jchemneu.2018.04.003.
[33]李强,阮怀珍,冯华.周细胞在出血性脑卒中中的作用[J].中华神经医学杂志,2015(10):1070-1073.DOI:10.3760/cma.j.issn.1671-8925.2015.10.022.
[34]Giannoni P,Badaut J,Dargazanli C,et al.The pericyte-glia interface at the blood-brain barrier[J].Clin Sci(Lond),2018,132(3):361-374.DOI:10.1042/CS20171634.
[35]Ozen I,Deierborg T,Miharada K,et al.Brain pericytes acquire a microglial phenotype after stroke[J].Acta Neuropathol,2014,128(3):381-396.DOI:10.1007/s00401-014-1295-x.
[36]Caspani EM,Crossley PH,Redondo-Garcia C,et al.Glioblastoma:a pathogenic crosstalk between tumor cells and pericytes[J].PLo S One,2014,9(7):e101402.DOI:10.1371/journal.pone.0101402.
[37]Ribeiro AL,Okamoto OK.Combined effects of pericytes in the tumor microenvironment[J].Stem Cells Int,2015:868475.DOI:10.1155/2015/868475.