Volume 10 Issue 4
Apr.  2019
Turn off MathJax
Article Contents
Chen Ling, Zunpeng Liu, Moshi Song, Weiqi Zhang, Si Wang, Xiaoqian Liu, Shuai Ma, Shuhui Sun, Lina Fu, Qun Chu, Juan Carlos Izpisua Belmonte, Zhaoxia Wang, Jing Qu, Yun Yuan, Guang-Hui Liu. Modeling CADASIL vascular pathologies with patient-derived induced pluripotent stem cells[J]. Protein&Cell, 2019, 10(4): 249-271. doi: 10.1007/s13238-019-0608-1
Citation: Chen Ling, Zunpeng Liu, Moshi Song, Weiqi Zhang, Si Wang, Xiaoqian Liu, Shuai Ma, Shuhui Sun, Lina Fu, Qun Chu, Juan Carlos Izpisua Belmonte, Zhaoxia Wang, Jing Qu, Yun Yuan, Guang-Hui Liu. Modeling CADASIL vascular pathologies with patient-derived induced pluripotent stem cells[J]. Protein&Cell, 2019, 10(4): 249-271. doi: 10.1007/s13238-019-0608-1

Modeling CADASIL vascular pathologies with patient-derived induced pluripotent stem cells

doi: 10.1007/s13238-019-0608-1

This work was supported by the National Key Research and Development Program of China (2018YFC2000100), the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA16010100), the National Key Research and Development Program of China (2017YFA0103304, 2017YFA0102802, 2018YFA0107203, 2016YFC1300605, 2015CB964800 and 2014CB910503), the National Natural Science Foundation of China (81625009, 81330008, 91749202, 91749123, 31671429, 81671377, 81771515, 31601109, 31601158, 81701388, 81601233, 81471414, 81870228, 81822018, 81801399, 31801010, 81801370, 81861168034 and 81471185), Program of Beijing Municipal Science and Technology Commission (Z151100003915072), Key Research Program of the Chinese Academy of Sciences (KJZDEWTZ-L05), Beijing Municipal Commission of Health and Family Planning (PXM2018_026283_000002), Advanced Innovation Center for Human Brain Protection (117212), and the State Key Laboratory of Membrane Biology.

  • Received Date: 2018-12-02
  • Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare hereditary cerebrovascular disease caused by a NOTCH3 mutation. However, the underlying cellular and molecular mechanisms remain unidentified. Here, we generated non-integrative induced pluripotent stem cells (iPSCs) from fibroblasts of a CADASIL patient harboring a heterozygous NOTCH3 mutation (c.3226C>T, p.R1076C). Vascular smooth muscle cells (VSMCs) differentiated from CADASIL-specific iPSCs showed gene expression changes associated with disease phenotypes, including activation of the NOTCH and NF-κB signaling pathway, cytoskeleton disorganization, and excessive cell proliferation. In comparison, these abnormalities were not observed in vascular endothelial cells (VECs) derived from the patient's iPSCs. Importantly, the abnormal upregulation of NF-κB target genes in CADASIL VSMCs was diminished by a NOTCH pathway inhibitor, providing a potential therapeutic strategy for CADASIL. Overall, using this iPSCbased disease model, our study identified clues for studying the pathogenic mechanisms of CADASIL and developing treatment strategies for this disease.
  • loading
  • [1]
    Agrinier N, Thilly N, Boivin JM, Dousset B, Alla F, Zannad F (2013) Prognostic value of serum PⅢNP, MMP1 and TIMP1 levels in hypertensive patients:a community-based prospective cohort study. Fundam Clin Pharmacol 27:572-580
    Anders S, Pyl PT, Huber W (2015) HTSeq-a python framework to work with high-throughput sequencing data. Bioinformatics 31:166-169
    Andersen P, Uosaki H, Shenje LT, Kwon C (2012) Non-canonical Notch signaling:emerging role and mechanism. Trends Cell Biol 22:257-265
    Andersson ER, Lendahl U (2014) Therapeutic modulation of Notch signalling-are we there yet? Nat Rev Drug Discov 13:357-378
    Andersson ER, Sandberg R, Lendahl U (2011) Notch signaling:simplicity in design, versatility in function. Development 138:3593-3612
    Ayaz F, Osborne BA (2014) Non-canonical notch signaling in cancer and immunity. Front Oncol 4:345
    Baker RG, Hayden MS, Ghosh S (2011) NF-kappaB, inflammation, and metabolic disease. Cell Metab 13:11-22
    Baron-Menguy C, Domenga-Denier V, Ghezali L, Faraci FM, Joutel A (2017) Increased Notch3 activity mediates pathological changes in structure of cerebral arteries. Hypertension 69:60-70
    Bin Q, Robert GN, Qing-Xiang Amy S (2009) ADAM19/adamalysin 19 structure, function, and role as a putative target in tumors and inflammatory diseases. Curr Pharm Des 15:2336-2348
    Bonnefoy A, Moura R, Hoylaerts MF (2008) The evolving role of thrombospondin-1 in hemostasis and vascular biology. Cell Mol Life Sci 65:713-727
    Brand K, Page S, Rogler G, Bartsch A, Brandl R, Knuechel R, Page M, Kaltschmidt C, Baeuerle PA, Neumeier D (1996) Activated transcription factor nuclear factor-kappa B is present in the atherosclerotic lesion. J Clin Investig 97:1715-1722
    Bray SJ (2016) Notch signalling in context. Nat Rev Mol Cell Biol 17:722
    Capone C, Cognat E, Ghezali L, Baron-Menguy C, Aubin D, Mesnard L, Stohr H, Domenga-Denier V, Nelson MT, Joutel A (2016) Reducing Timp3 or vitronectin ameliorates disease manifestations in CADASIL mice. Ann Neurol 79:387-403
    Chabriat H, Pappata S, Ostergaard L, Clark CA, Pachot-Clouard M, Vahedi K, Jobert A, Le Bihan D, Bousser MG (2000) Cerebral hemodynamics in CADASIL before and after acetazolamide challenge assessed with MRI bolus tracking. Stroke 31:1904-1912
    Chen JH, Vercamer C, Li Z, Paulin D, Vandenbunder B, Stehelin D (1996) PEA3 transactivates vimentin promoter in mammary epithelial and tumor cells. Oncogene 13:1667-1675
    Chistiakov DA, Orekhov AN, Bobryshev YV (2015) Vascular smooth muscle cell in atherosclerosis. Acta Physiol 214:33-50
    Craggs LJ, Fenwick R, Oakley AE, Ihara M, Kalaria RN (2015) Immunolocalization of platelet-derived growth factor receptorbeta (PDGFR-beta) and pericytes in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Neuropathol Appl Neurobiol 41:557-570
    Di Donato I, Bianchi S, De Stefano N, Dichgans M, Dotti MT, Duering M, Jouvent E, Korczyn AD, Lesnik-Oberstein SA, Malandrini A et al (2017) Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) as a model of small vessel disease:update on clinical, diagnostic, and management aspects. BMC Med 15:41
    Dinh QN, Drummond GR, Sobey CG, Chrissobolis S (2014) Roles of inflammation, oxidative stress, and vascular dysfunction in hypertension. Biomed Res Int 2014:406960
    Dollery CM, Libby P (2006) Atherosclerosis and proteinase activation. Cardiovasc Res 69:625-635
    Domenga V, Fardoux P, Lacombe P, Monet M, Maciazek J, Krebs LT, Klonjkowski B, Berrou E, Mericskay M, Li Z et al (2004) Notch3 is required for arterial identity and maturation of vascular smooth muscle cells. Genes Dev 18:2730-2735
    Donahue CP, Kosik KS (2004) Distribution pattern of Notch3 mutations suggests a gain-of-function mechanism for CADASIL. Genomics 83:59-65
    Dong H, Blaivas M, Wang MM (2012) Bidirectional encroachment of collagen into the tunica media in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Brain Res 1456:64-71
    Duan S, Yuan G, Liu X, Ren R, Li J, Zhang W, Wu J, Xu X, Fu L, Li Y et al (2015) PTEN deficiency reprogrammes human neural stem cells towards a glioblastoma stem cell-like phenotype. Nat Commun 6:10068
    Duering M, Karpinska A, Rosner S, Hopfner F, Zechmeister M, Peters N, Kremmer E, Haffner C, Giese A, Dichgans M et al(2011) Co-aggregate formation of CADASIL-mutant NOTCH3:a single-particle analysis. Hum Mol Genet 20:3256-3265
    Edwards DR, Handsley MM, Pennington CJ (2008) The ADAM metalloproteinases. Mol Aspects Med 29:258-289
    Fang XJ, Yu M, Wu Y, Zhang ZH, Wang WW, Wang ZX, Yuan Y (2017) Study of enhanced depth imaging optical coherence tomography in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Chin Med J (Engl) 130:1042-1048
    Fletcher DA, Mullins RD (2010) Cell mechanics and the cytoskeleton. Nature 463:485-492
    Fogl C, Mohammed F, Al-Jassar C, Jeeves M, Knowles TJ, Rodriguez-Zamora P, White SA, Odintsova E, Overduin M, Chidgey M (2016) Mechanism of intermediate filament recognition by plakin repeat domains revealed by envoplakin targeting of vimentin. Nat Commun 7:10827
    Fu L, Xu X, Ren R, Wu J, Zhang W, Yang J, Ren X, Wang S, Zhao Y, Sun L et al (2016) Modeling xeroderma pigmentosum associated neurological pathologies with patients-derived iPSCs. Protein Cell 7:210-221
    Fuertes-Alvarez S, Maeso-Alonso L, Villoch-Fernandez J, Wildung M, Martin-Lopez M, Marshall C, Villena-Cortes AJ, Diez-Prieto I, Pietenpol JA, Tissir F et al (2018) p73 regulates ependymal planar cell polarity by modulating actin and microtubule cytoskeleton. Cell Death Dis 9:1183
    Gatti JR, Zhang X, Korcari E, Lee SJ, Greenstone N, Dean JG, Maripudi S, Wang MM (2018) Redistribution of mature smooth muscle markers in brain arteries in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Transl Stroke Res. https://doi.org/10.1007/
    s12975-018-0643-x Geng L, Liu Z, Zhang W, Li W, Wu Z, Wang W, Ren R, Su Y, Wang P, Sun L et al (2018) Chemical screen identifies a geroprotective role of quercetin in premature aging. Protein Cell. https://doi.org/10.1007/s13238-018-0567-y
    Ghosh M, Balbi M, Hellal F, Dichgans M, Lindauer U, Plesnila N (2015) Pericytes are involved in the pathogenesis of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Ann Neurol 78:887-900
    Goate AM, Morris JC (1997) Notch3 mutations and the potential for diagnostic testing for CADASIL. Lancet (Lond, Engl) 350:1490
    Granata A, Bernard WG, Zhao N, McCafferty J, Lilly B, Sinha S (2015) Temporal and embryonic lineage-dependent regulation of human vascular SMC development by NOTCH3. Stem Cells Dev 24:846-856
    Gu X, Liu XY, Fagan A, Gonzalez-Toledo ME, Zhao LR (2012) Ultrastructural changes in cerebral capillary pericytes in aged Notch3 mutant transgenic mice. Ultrastruct Pathol 36:48-55
    Guruharsha KG, Kankel MW, Artavanis-Tsakonas S (2012) The Notch signalling system:recent insights into the complexity of a conserved pathway. Nat Rev Genet 13:654-666
    Haritunians T, Chow T, De Lange RP, Nichols JT, Ghavimi D, Dorrani N, St Clair DM, Weinmaster G, Schanen C (2005) Functional analysis of a recurrent missense mutation in Notch3 in CADASIL. J Neurol Neurosurg Psychiatry 76:1242-1248
    Henrion D, Terzi F, Matrougui K, Duriez M, Boulanger CM, ColucciGuyon E, Babinet C, Briand P, Friedlander G, Poitevin P et al(1997) Impaired flow-induced dilation in mesenteric resistance arteries from mice lacking vimentin. J Clin Investig 100:2909-2914
    Herve D, Chabriat H (2010) Cadasil. J Geriatr Psychiatry Neurol 23:269-276
    Jin Y, Kaluza D, Jakobsson L (2014) VEGF, Notch and TGFbeta/BMPs in regulation of sprouting angiogenesis and vascular patterning. Biochem Soc Trans 42:1576-1583
    Joutel A (2011) Pathogenesis of CADASIL:transgenic and knockout mice to probe function and dysfunction of the mutated gene, Notch3, in the cerebrovasculature. BioEssays 33:73-80
    Joutel A, Corpechot C, Ducros A, Vahedi K, Chabriat H, Mouton P, Alamowitch S, Domenga V, Cecillion M, Marechal E et al (1996) Notch3 mutations in CADASIL, a hereditary adult-onset condition causing stroke and dementia. Nature 383:707-710
    Joutel A, Monet-Lepretre M, Gosele C, Baron-Menguy C, Hammes A, Schmidt S, Lemaire-Carrette B, Domenga V, Schedl A, Lacombe P et al (2010) Cerebrovascular dysfunction and microcirculation rarefaction precede white matter lesions in a mouse genetic model of cerebral ischemic small vessel disease.
    J Clin Invest 120:433-445
    Joutel A, Vahedi K, Corpechot C, Troesch A, Chabriat H, Vayssière C, Cruaud C, Maciazek J, Weissenbach J, Bousser M-G et al(1997) Strong clustering and stereotyped nature of Notch3 mutations in CADASIL patients. Lancet 350:1511-1515
    Jung JH, Fu X, Yang PC (2017) Exosomes generated from iPSCderivatives:new direction for stem cell therapy in human heart diseases. Circ Res 120:407-417
    Kassianidou E, Kumar S (2015) A biomechanical perspective on stress fiber structure and function. Biochim Biophys Acta 1853:3065-3074
    Killeen MJ, Linder M, Pontoniere P, Crea R (2014) NF-κβ signaling and chronic inflammatory diseases:exploring the potential of natural products to drive new therapeutic opportunities. Drug Discov Today 19:373-378
    Kim D, Langmead B, Salzberg SL (2015) HISAT:a fast spliced aligner with low memory requirements. Nat Methods 12:357-360
    Kim W-J, Kang Y-J, Suk K, Park J-E, Kwon BS, Lee W-H (2008) Comparative analysis of the expression patterns of various TNFSF/TNFRSF in atherosclerotic plaques. Immunol Invest 37:359-373
    Kopan R, Ilagan MX (2009) The canonical Notch signaling pathway:unfolding the activation mechanism. Cell 137:216-233
    Krings T, Mandell DM, Kiehl TR, Geibprasert S, Tymianski M, Alvarez H, terBrugge KG, Hans FJ (2011) Intracranial aneurysms:from vessel wall pathology to therapeutic approach. Nat Rev Neurol 7:547-559
    Krishna SM, Golledge J (2013) The role of thrombospondin-1 in cardiovascular health and pathology. Int J Cardiol 168:692-706
    Lacombe P, Oligo C, Domenga V, Tournier-Lasserve E, Joutel A (2005) Impaired cerebral vasoreactivity in a transgenic mouse model of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy arteriopathy. Stroke 36:1053-1058
    Lee KE, Jee HM, Hong JY, Kim MN, Oh MS, Kim YS, Kim KW, Kim KE, Sohn MH (2018) German cockroach extract induces matrix metalloproteinase-1 expression, leading to tight junction disruption in human airway epithelial cells. Yonsei Med J 59:1222-1231
    Li M, Izpisua Belmonte JC (2016) Looking to the future following 10 years of induced pluripotent stem cell technologies. Nat Protoc 11:1579-1585
    Li M, Suzuki K, Qu J, Saini P, Dubova I, Yi F, Lee J, Sancho-Martinez I, Liu GH, Izpisua Belmonte JC (2011) Efficient correction of hemoglobinopathy-causing mutations by homologous recombination in integration-free patient iPSCs. Cell Res 21:1740-1744
    Li R, Fang F, Jiang M, Wang C, Ma J, Kang W, Zhang Q, Miao Y, Wang D, Guo Y et al (2017) STAT3 and NF-κB are simultaneously suppressed in dendritic cells in lung cancer. Sci Rep 7:45395
    Li X, Zhang X, Leathers R, Makino A, Huang C, Parsa P, Macias J, Yuan JX, Jamieson SW, Thistlethwaite PA (2009) Notch3 signaling promotes the development of pulmonary arterial hypertension. Nat Med 15:1289-1297
    Liu GH, Barkho BZ, Ruiz S, Diep D, Qu J, Yang SL, Panopoulos AD, Suzuki K, Kurian L, Walsh C et al (2011a) Recapitulation of premature ageing with iPSCs from Hutchinson-Gilford progeria syndrome. Nature 472:221-225
    Liu GH, Qu J, Suzuki K, Nivet E, Li M, Montserrat N, Yi F, Xu X, Ruiz S, Zhang W et al (2012) Progressive degeneration of human neural stem cells caused by pathogenic LRRK2. Nature 491:603-607
    Liu GH, Suzuki K, Li M, Qu J, Montserrat N, Tarantino C, Gu Y, Yi F, Xu X, Zhang W et al (2014) Modelling Fanconi anemia pathogenesis and therapeutics using integration-free patient-derived iPSCs. Nat Commun 5:4330
    Liu GH, Suzuki K, Qu J, Sancho-Martinez I, Yi F, Li M, Kumar S, Nivet E, Kim J, Soligalla RD et al (2011b) Targeted gene correction of laminopathy-associated LMNA mutations in patientspecific iPSCs. Cell Stem Cell 8:688-694
    Liu H, Zhang W, Kennard S, Caldwell RB, Lilly B (2010) Notch3 is critical for proper angiogenesis and mural cell investment. Circ Res 107:860-870
    Lontchi-Yimagou E, Sobngwi E, Matsha TE, Kengne AP (2013) Diabetes mellitus and inflammation. Curr Diabetes Rep 13:435-444
    Love MI, Huber W, Anders S (2014) Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol 15:550
    Lyon CA, Wadey KS, George SJ (2016) Soluble N-cadherin:a novel inhibitor of VSMC proliferation and intimal thickening. Vascul Pharmacol 78:53-62
    Meng H, Zhang X, Yu G, Lee SJ, Chen YE, Prudovsky I, Wang MM (2012) Biochemical characterization and cellular effects of CADASIL mutants of NOTCH3. PLoS ONE 7:e44964
    Miao Q, Paloneva T, Tuisku S, Roine S, Poyhonen M, Viitanen M, Kalimo H (2006) Arterioles of the lenticular nucleus in CADASIL. Stroke 37:2242-2247
    Miao Q, Paloneva T, Tuominen S, Poyhonen M, Tuisku S, Viitanen M, Kalimo H (2004) Fibrosis and stenosis of the long penetrating cerebral arteries:the cause of the white matter pathology in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Brain Pathol 14:358-364
    Monet-Lepretre M, Haddad I, Baron-Menguy C, Fouillot-Panchal M, Riani M, Domenga-Denier V, Dussaule C, Cognat E, Vinh J, Joutel A (2013) Abnormal recruitment of extracellular matrix proteins by excess Notch3 ECD:a new pathomechanism in CADASIL. Brain 136:1830-1845
    Moreton FC, Cullen B, Delles C, Santosh C, Gonzalez RL, Dani K, Muir KW (2017) Vasoreactivity in CADASIL:comparison to structural MRI and neuropsychology. J Cereb Blood Flow Metab 1:1-2. https://doi.org/10.1177/0271678X17710375
    Natarajan K, Singh S, Burke TR Jr, Grunberger D, Aggarwal BB (1996) Caffeic acid phenethyl ester is a potent and specific inhibitor of activation of nuclear transcription factor NF-kappa B. Proc Natl Acad Sci USA 93:9090-9095
    Noseda M, Fu Y, Niessen K, Wong F, Chang L, McLean G, Karsan A (2006) Smooth Muscle alpha-actin is a direct target of Notch/CSL. Circ Res 98:1468-1470
    Okeda R, Arima K, Kawai M (2002) Arterial changes in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) in relation to pathogenesis of diffuse myelin loss of cerebral white matter:examination of cerebral medullary arteries by reconstruction of serial sections of an autopsy case. Stroke 33:2565-2569
    Okita K, Matsumura Y, Sato Y, Okada A, Morizane A, Okamoto S, Hong H, Nakagawa M, Tanabe K, Tezuka K et al (2011) A more efficient method to generate integration-free human iPS cells. Nat Methods 8:409-412
    Panahi M, Yousefi Mesri N, Samuelsson E-B, Coupland KG, Forsell C, Graff C, Tikka S, Winblad B, Viitanen M, Karlström H et al(2018) Differences in proliferation rate between CADASIL and control vascular smooth muscle cells are related to increased TGFβ expression. J Cell Mol Med 22:3016-3024
    Patsch C, Challet-Meylan L, Thoma EC, Urich E, Heckel T, O'Sullivan JF, Grainger SJ, Kapp FG, Sun L, Christensen K et al (2015) Generation of vascular endothelial and smooth muscle cells from human pluripotent stem cells. Nat Cell Biol 17:994-1003
    Penn DL, Witte SR, Komotar RJ, Sander Connolly E Jr (2014) The role of vascular remodeling and inflammation in the pathogenesis of intracranial aneurysms. J Clin Neurosci 21:28-32
    Penton AL, Leonard LD, Spinner NB (2012) Notch signaling in human development and disease. Semin Cell Dev Biol 23:450-457
    Pfefferkorn T, von Stuckrad-Barre S, Herzog J, Gasser T, Hamann GF, Dichgans M (2001) Reduced cerebrovascular CO(2) reactivity in CADASIL:a transcranial Doppler sonography study. Stroke 32:17-21
    Rogers NM, Ghimire K, Calzada MJ, Isenberg JS (2017) Matricellular protein thrombospondin-1 in pulmonary hypertension:multiple pathways to disease. Cardiovasc Res 113:858-868
    Ruan ZB, Fu XL, Li W, Ye J, Wang RZ, Zhu L (2016) Effect of notch1,2,3 genes silicing on NF-kappaB signaling pathway of macrophages in patients with atherosclerosis. Biomed Pharmacother 84:666-673
    Ruchoux MM, Chabriat H, Bousser MG, Baudrimont M, TournierLasserve E (1994) Presence of ultrastructural arterial lesions in muscle and skin vessels of patients with CADASIL. Stroke 25:2291-2292
    Ruchoux MM, Maurage CA (1998) Endothelial changes in muscle and skin biopsies in patients with CADASIL. Neuropathol Appl Neurobiol 24:60-65
    Rudijanto A (2007) The role of vascular smooth muscle cells on the pathogenesis of atherosclerosis. Acta Med Indones 39:86-93
    Rutten JW, Dauwerse HG, Peters DJ, Goldfarb A, Venselaar H, Haffner C, van Ommen GJ, Aartsma-Rus AM, Lesnik Oberstein SA (2016) Therapeutic NOTCH3 cysteine correction in CADASIL using exon skipping:in vitro proof of concept. Brain 139:1123-1135
    Rutten JW, Haan J, Terwindt GM, van Duinen SG, Boon EM, Lesnik Oberstein SA (2014) Interpretation of NOTCH3 mutations in the diagnosis of CADASIL. Expert Rev Mol Diagn 14:593-603
    Shibata M, Ohtani R, Ihara M, Tomimoto H (2004) White matter lesions and glial activation in a novel mouse model of chronic cerebral hypoperfusion. Stroke 35:2598-2603
    Shin HM, Minter LM, Cho OH, Gottipati S, Fauq AH, Golde TE, Sonenshein GE, Osborne BA (2006) Notch1 augments NFkappaB activity by facilitating its nuclear retention. EMBO J 25:129-138
    Shin HM, Tilahun ME, Cho OH, Chandiran K, Kuksin CA, Keerthivasan S, Fauq AH, Golde TE, Miele L, Thome M et al(2014) NOTCH1 can initiate NF-kappaB activation via cytosolic interactions with components of the T cell signalosome. Front Immunol 5:249
    Siebel C, Lendahl U (2017) Notch signaling in development, tissue homeostasis, and disease. Physiol Rev 97:1235-1294
    Siggers T, Gilmore TD, Barron B, Penvose A (2015) Characterizing the DNA binding site specificity of NF-kappaB with proteinbinding microarrays (PBMs). Methods Mol Biol (Clifton, NJ) 1280:609-630
    Song Y, Zhang Y, Jiang H, Zhu Y, Liu L, Feng W, Yang L, Wang Y, Li M (2015) Activation of Notch3 promotes pulmonary arterial smooth muscle cells proliferation via Hes1/p27Kip1 signaling pathway. FEBS Open Bio 5:656-660
    Subramanian A, Kuehn H, Gould J, Tamayo P, Mesirov JP (2007) GSEA-P:a desktop application for gene set enrichment analysis. Bioinformatics 23:3251-3253
    Sweeney C, Morrow D, Birney YA, Coyle S, Hennessy C, Scheller A, Cummins PM, Walls D, Redmond EM, Cahill PA (2004) Notch 1 and 3 receptor signaling modulates vascular smooth muscle cell growth, apoptosis, and migration via a CBF-1/RBP-Jk dependent pathway. FASEB J 18:1421-1423
    Swift MR, Weinstein BM (2009) Arterial-venous specification during development. Circ Res 104:576-588
    Takahashi K, Adachi K, Yoshizaki K, Kunimoto S, Kalaria RN, Watanabe A (2010) Mutations in NOTCH3 cause the formation and retention of aggregates in the endoplasmic reticulum, leading to impaired cell proliferation. Hum Mol Genet 19:79-89
    Tikka S, Mykkanen K, Ruchoux MM, Bergholm R, Junna M, Poyhonen M, Yki-Jarvinen H, Joutel A, Viitanen M, Baumann M et al (2009) Congruence between NOTCH3 mutations and GOM in 131 CADASIL patients. Brain 132:933-939
    Tikka S, Ng YP, Di Maio G, Mykkanen K, Siitonen M, Lepikhova T, Poyhonen M, Viitanen M, Virtanen I, Kalimo H et al (2012) CADASIL mutations and shRNA silencing of NOTCH3 affect actin organization in cultured vascular smooth muscle cells. J Cereb Blood Flow Metab 32:2171-2180
    Tripathi S, Pohl MO, Zhou Y, Rodriguez-Frandsen A, Wang G, Stein DA, Moulton HM, DeJesus P, Che J, Mulder LCF et al (2015) Meta-and orthogonal integration of influenza "OMICs" data defines a role for UBR4 in virus budding. Cell Host Microbe 18:723-735
    Trivedi V, Boire A, Tchernychev B, Kaneider NC, Leger AJ, O'Callaghan K, Covic L, Kuliopulos A (2009) Platelet matrix metalloprotease-1 mediates thrombogenesis by activating PAR1 at a cryptic ligand site. Cell 137:332-343
    Tu HQ, Qin XH, Liu ZB, Song ZQ, Hu HB, Zhang YC, Chang Y, Wu M, Huang Y, Bai YF et al (2018) Microtubule asters anchored by FSD1 control axoneme assembly and ciliogenesis. Nat Commun 9:5277
    Vacca A, Felli MP, Palermo R, Di Mario G, Calce A, Di Giovine M, Frati L, Gulino A, Screpanti I (2006) Notch3 and pre-TCR interaction unveils distinct NF-kappaB pathways in T-cell development and leukemia. EMBO J 25:1000-1008
    Venkatesh D, Fredette N, Rostama B, Tang Y, Vary CP, Liaw L, Urs S (2011) RhoA-mediated signaling in Notch-induced senescence-like growth arrest and endothelial barrier dysfunction. Arterioscler Thromb Vasc Biol 31:876-882
    Viitanen M, Sundstrom E, Baumann M, Poyhonen M, Tikka S, Behbahani H (2013) Experimental studies of mitochondrial function in CADASIL vascular smooth muscle cells. Exp Cell Res 319:134-143
    Villa N, Walker L, Lindsell CE, Gasson J, Iruela-Arispe ML, Weinmaster G (2001) Vascular expression of Notch pathway receptors and ligands is restricted to arterial vessels. Mech Dev 108:161-164
    Viola J, Soehnlein O (2015) Atherosclerosis-a matter of unresolved inflammation. Semin Immunol 27:184-193
    Wang L, Yi F, Fu L, Yang J, Wang S, Wang Z, Suzuki K, Sun L, Xu X, Yu Y et al (2017) CRISPR/Cas9-mediated targeted gene correction in amyotrophic lateral sclerosis patient iPSCs. Protein Cell 8:365-378
    Wang MM (2018) Cadasil. Handb Clin Neurol 148:733-743
    Wang P, Liu Z, Zhang X, Li J, Sun L, Ju Z, Li J, Chan P, Liu G-H, Zhang W et al (2018a) CRISPR/Cas9-mediated gene knockout reveals a guardian role of NF-κB/RelA in maintaining the homeostasis of human vascular cells. Protein Cell 9:945-965
    Wang S, Hu B, Ding Z, Dang Y, Wu J, Li D, Liu X, Xiao B, Zhang W, Ren R et al (2018b) ATF6 safeguards organelle homeostasis and cellular aging in human mesenchymal stem cells. Cell Discov 4:2
    Wang Z, Yuan Y, Zhang W, Lv H, Hong D, Chen B, Liu Y, Luan X, Xie S, Wu S (2011) NOTCH3 mutations and clinical features in 33 mainland Chinese families with CADASIL. J Neurol Neurosurg Psychiatry 82:534-539
    Wu JR, Yeh JL, Liou SF, Dai ZK, Wu BN, Hsu JH (2016) Gammasecretase inhibitor prevents proliferation and migration of ductus arteriosus smooth muscle cells through the Notch3-HES1/2/5 pathway. Int J Biol Sci 12:1063-1073
    Wu Z, Zhang W, Song M, Wang W, Wei G, Li W, Lei J, Huang Y, Sang Y, Chan P et al (2018) Differential stem cell aging kinetics in Hutchinson-Gilford progeria syndrome and Werner syndrome. Protein Cell 9:333-350
    Xu CY, Qin MB, Tan L, Liu SQ, Huang JA (2016) NIBP impacts on the expression of E-cadherin, CD44 and vimentin in colon cancer via the NF-kappaB pathway. Mol Med Rep 13:5379-5385
    Yamin R, Morgan KG (2012) Deciphering actin cytoskeletal function in the contractile vascular smooth muscle cell. J Physiol 590:4145-4154
    Yang J, Li J, Suzuki K, Liu X, Wu J, Zhang W, Ren R, Zhang W, Chan P, Izpisua Belmonte JC et al (2017) Genetic enhancement in cultured human adult stem cells conferred by a single nucleotide recoding. Cell Res 27:1178-1181
    Ye L, Chang YH, Xiong Q, Zhang P, Zhang L, Somasundaram P, Lepley M, Swingen C, Su L, Wendel JS et al (2014) Cardiac repair in a porcine model of acute myocardial infarction with human induced pluripotent stem cell-derived cardiovascular cells. Cell Stem Cell 15:750-761
    Zhang W, Li J, Suzuki K, Qu J, Wang P, Zhou J, Liu X, Ren R, Xu X, Ocampo A et al (2015a) Aging stem cells. A Werner syndrome stem cell model unveils heterochromatin alterations as a driver of human aging. Science 348:1160-1163
    Zhang W, Song M, Qu J, Liu GH (2018a) Epigenetic modifications in cardiovascular aging and diseases. Circ Res 123:773-786
    Zhang X, Lee SJ, Young MF, Wang MM (2015b) The small leucinerich proteoglycan BGN accumulates in CADASIL and binds to NOTCH3. Transl Stroke Res 6:148-155
    Zhang Y, Zhou S, Deng F, Chen X, Wang X, Wang Y, Zhang H, Dai W, He B, Zhang Q et al (2018b) The function and mechanism of preactivated thiomers in triggering epithelial tight junctions opening. Eur J Pharm Biopharm 133:188-199
  • 加载中


    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索


    Article Metrics

    Article views (810) PDF downloads(62) Cited by()
    Proportional views


    DownLoad:  Full-Size Img  PowerPoint