{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T10:56:21Z","timestamp":1769165781635,"version":"3.49.0"},"reference-count":91,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,7,14]],"date-time":"2021-07-14T00:00:00Z","timestamp":1626220800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008949","name":"Uniscientia Stiftung","doi-asserted-by":"publisher","award":["P100-2016"],"award-info":[{"award-number":["P100-2016"]}],"id":[{"id":"10.13039\/501100008949","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["31003A-138067"],"award-info":[{"award-number":["31003A-138067"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Many pathological conditions of the brain are associated with structural abnormalities within the neurovascular system and linked to pericyte (PC) loss and\/or dysfunction. Since crosstalk between endothelial cells (ECs) and PCs greatly impacts the function of the blood\u2013brain barrier (BBB), effects of PCs on endothelial integrity and function have been investigated extensively. However, the impact of ECs on the function and activity of PCs remains largely unknown. Hence, using co-cultures of human brain vascular PCs with human cerebral microvascular ECs on opposite sides of porous Transwell inserts which facilitates direct EC\u2013PC contact and improves EC barrier function, we analyzed EC-driven transcriptomic changes in PCs using microarrays and changes in cytokines\/chemokines using proteome arrays. Gene expression analysis (GEA) in PCs co-cultured with ECs versus PCs cultured alone showed significant upregulation of 1\u2032334 genes and downregulation of 964 genes. GEA in co-cultured PCs revealed increased expression of five prominent PC markers as well as soluble factors, such as transforming growth factor beta, fibroblast growth factor, angiopoietin 1, brain-derived neurotrophic factor, all of which are involved in EC\u2013PC crosstalk and BBB induction. Pathway enrichment analysis of modulated genes showed a strong impact on many inflammatory and extracellular matrix (ECM) pathways including interferon and interleukin signaling, TGF-\u03b2 and interleukin-1 regulation of ECM, as well as on the mRNA processing pathway. Interestingly, while co-culture induced the mRNA expression of many chemokines and cytokines, including several CCL- and CXC-motif ligands and interleukins, we observed a decreased expression of the same inflammatory mediators on the protein level. Importantly, in PCs, ECs significantly induced interferon associated proteins (IFIT1, IFI44L, IF127, IFIT3, IFI6, IFI44) with anti-viral actions; downregulated prostaglandin E receptor 2 (prevent COX-2 mediated BBB damage); upregulated fibulin-3 and connective tissue growth factor essential for BBB integrity; and multiple ECMs (collagens and integrins) that inhibit cell migration. Our findings suggest that via direct contact, ECs prime PCs to induce molecules to promote BBB integrity and cell survival during infection and inflammatory insult. Taken together, we provide first evidence that interaction with ECs though porous membranes induces major changes in the transcriptomic and proteomic profile of PCs. ECs influence genes involved in diverse aspects of PC function including PC maturation, cell survival, anti-viral defense, blood flow regulation, immuno-modulation and ECM deposition.<\/jats:p>","DOI":"10.3390\/cells10071784","type":"journal-article","created":{"date-parts":[[2021,7,14]],"date-time":"2021-07-14T21:56:51Z","timestamp":1626299811000},"page":"1784","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Transcriptomic Analysis of Human Brain -Microvascular Endothelial Cell Driven Changes in -Vascular Pericytes"],"prefix":"10.3390","volume":"10","author":[{"given":"Lisa","family":"Kurmann","sequence":"first","affiliation":[{"name":"Department of Reproductive Endocrinology, University Hospital Zurich, 8952 Schlieren, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4722-4506","authenticated-orcid":false,"given":"Michal","family":"Okoniewski","sequence":"additional","affiliation":[{"name":"ID Scientific IT Services, ETH Zurich, 8092 Zurich, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raghvendra","family":"Dubey","sequence":"additional","affiliation":[{"name":"Department of Reproductive Endocrinology, University Hospital Zurich, 8952 Schlieren, Switzerland"},{"name":"Department of Pharmacology & Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15219, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1038\/nn.4288","article-title":"Pericytes of the neurovascular unit: Key functions and signaling pathways","volume":"19","author":"Sweeney","year":"2016","journal-title":"Nat. Neurosci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1038\/nature09513","article-title":"Pericytes are required for blood-brain barrier integrity during embryogenesis","volume":"468","author":"Daneman","year":"2010","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.devcel.2011.07.001","article-title":"Pericytes: Developmental, Physiological, and Pathological Perspectives, Problems, and Promises","volume":"21","author":"Armulik","year":"2011","journal-title":"Dev. Cell"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Sweeney, M., and Foldes, G. (2018). Takes Two: Endothelial-Perivascular Cell Cross-Talk in Vascular Development and Disease. Front. Cardiovasc. Med., 5.","DOI":"10.3389\/fcvm.2018.00154"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e48070","DOI":"10.15252\/embr.201948070","article-title":"Emerging links between cerebrovascular and neurodegenerative diseases-a special role for pericytes","volume":"20","author":"Lendahl","year":"2019","journal-title":"EMBO Rep."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Ribeiro, A.L., and Okamoto, O.K. (2015). Combined Effects of Pericytes in the Tumor Microenvironment. Stem Cells Int., 2015.","DOI":"10.1155\/2015\/868475"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1161\/01.RES.0000182903.16652.d7","article-title":"Endothelial\/pericyte interactions","volume":"97","author":"Armulik","year":"2005","journal-title":"Circ. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.cjtee.2020.02.006","article-title":"Research advances in pericyte function and their roles in diseases","volume":"23","author":"Zhang","year":"2020","journal-title":"Chin. J. Traumatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1017\/S1431927611012402","article-title":"Endothelial Cell-Pericyte Interactions Stimulate Basement Membrane Matrix Assembly: Influence on Vascular Tube Remodeling, Maturation, and Stabilization","volume":"18","author":"Stratman","year":"2012","journal-title":"Microsc. Microanal."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1002\/dneu.20954","article-title":"Extracellular Matrix and Matrix Receptors in Blood-Brain Barrier Formation and Stroke","volume":"71","author":"Baeten","year":"2011","journal-title":"Dev. Neurobiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2390","DOI":"10.1002\/jnr.24715","article-title":"Beyond barrier functions: Roles of pericytes in homeostasis and regulation of neuroinflammation","volume":"98","author":"Bhattacharya","year":"2020","journal-title":"J. Neurosci. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.brainres.2014.01.004","article-title":"Brain capillary pericytes contribute to the immune defense in response to cytokines or LPS in vitro","volume":"1550","author":"Pieper","year":"2014","journal-title":"Brain Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.pharmthera.2016.11.008","article-title":"Pericytes, an overlooked player in vascular pathobiology","volume":"171","author":"Slater","year":"2017","journal-title":"Pharmacol. Ther."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1111\/bpa.12152","article-title":"The Pericyte: A Forgotten Cell Type with Important Implications for Alzheimer\u2019s Disease?","volume":"24","author":"Winkler","year":"2014","journal-title":"Brain Pathol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Navarro, R., Compte, M., Alvarez-Vallina, L., and Sanz, L. (2016). Immune Regulation by Pericytes: Modulating Innate and Adaptive Immunity. Front. Immunol., 7.","DOI":"10.3389\/fimmu.2016.00480"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"23551","DOI":"10.1073\/pnas.1913373116","article-title":"Pericytes enable effective angiogenesis in the presence of proinflammatory signals","volume":"116","author":"Kang","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Smyth, L.C.D., Rustenhoven, J., Park, T.I.H., Schweder, P., Jansson, D., Heppner, P.A., O\u2019Carroll, S.J., Mee, E.W., Faull, R.L.M., and Curtis, M. (2018). Unique and shared inflammatory profiles o human brain endothelia and pericytes. J. Neuroinflamm., 15.","DOI":"10.1186\/s12974-018-1167-8"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Kurmann, L., Okoniewski, M., Ogunshola, O.O., Leeners, B., Imthurn, B., and Dubey, R.K. (2021). Transcryptomic Analysis of Human Brain-Microvascular Endothelial Response to -Pericytes: Cell Orientation Defines Barrier Function. Cells, 10.","DOI":"10.3390\/cells10040963"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1872","DOI":"10.1096\/fj.04-3458fje","article-title":"Blood-brain barrier-specific properties of a human adult brain endothelial cell line","volume":"19","author":"Weksler","year":"2005","journal-title":"FASEB J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"7222","DOI":"10.7150\/thno.32058","article-title":"Generation of human induced pluripotent stem cell-derived cardiomyocytes in 2D monolayer and scalable 3D suspension bioreactor cultures with reduced batch-to-batch variations","volume":"9","author":"Hamad","year":"2019","journal-title":"Theranostics"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Huang, R., Grishagin, I., Wang, Y., Zhao, T., Greene, J., Obenauer, J.C., Ngan, D., Dac-Trung, N., Guha, R., and Jadhav, A. (2019). The NCATS BioPlanet\u2014An Integrated Platform for Exploring the Universe of Cellular Signaling Pathways for Toxicology, Systems Biology, and Chemical Genomics. Front. Pharmacol., 10.","DOI":"10.3389\/fphar.2019.00445"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"15586","DOI":"10.1038\/s41598-019-51838-x","article-title":"Transcriptome analysis reveals microvascular endothelial cell-dependent pericyte differentiation","volume":"9","author":"Brandt","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"35108","DOI":"10.1038\/srep35108","article-title":"Analysis of the brain mural cell transcriptome","volume":"6","author":"He","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1398","DOI":"10.1038\/nn.2946","article-title":"Central nervous system pericytes in health and disease","volume":"14","author":"Winkler","year":"2011","journal-title":"Nat. Neurosci."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Heymans, M., Figueiredo, R., Dehouck, L., Francisco, D., Sano, Y., Shimizu, F., Kanda, T., Bruggmann, R., Engelhardt, B., and Winter, P. (2020). Contribution of brain pericytes in blood-brain barrier formation and maintenance: A transcriptomic study of cocultured human endothelial cells derived from hematopoietic stem cells. Fluids Barriers CNS, 17.","DOI":"10.1186\/s12987-020-00208-1"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Jamieson, J.J., Linville, R.M., Ding, Y.Y., Gerecht, S., and Searson, P.C. (2019). Role of iPSC-derived pericytes on barrier function of iPSC-derived brain microvascular endothelial cells in 2D and 3D. Fluids Barriers CNS, 16.","DOI":"10.1186\/s12987-019-0136-7"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1080\/10739680590904955","article-title":"Differential arterial\/venous expression of NG2 proteoglycan in perivascular cells along microvessels: Identifying a venule-specific phenotype","volume":"12","author":"Murfee","year":"2005","journal-title":"Microcirculation"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Jansson, D., Rustenhoven, J., Feng, S., Hurley, D., Oldfield, R.L., Bergin, P.S., Mee, E.W., Faull, R.L.M., and Dragunow, M. (2015). A role for human brain pericytes in neuroinflammation (vol 11, 104, 2014). J. NeuroInflamm., 12.","DOI":"10.1186\/1742-2094-11-104"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.neuron.2008.01.003","article-title":"The blood-brain barrier in health and chronic neurodegenerative disorders","volume":"57","author":"Zlokovic","year":"2008","journal-title":"Neuron"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2457","DOI":"10.1074\/jbc.M113.521161","article-title":"Lipopolysaccharide Activates Toll-like Receptor 4 (TLR4)-mediated NF-kappa B Signaling Pathway and Proinflammatory Response in Human Pericytes","volume":"289","author":"Compte","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/S0008-6363(02)00512-6","article-title":"TLR4-mediated inflammatory activation of human coronary artery endothelial cells by LPS","volume":"56","author":"Zeuke","year":"2002","journal-title":"Cardiovasc. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.neuron.2018.08.030","article-title":"PDGFR beta Cells Rapidly Relay Inflammatory Signal from the Circulatory System to Neurons via Chemokine CCL2","volume":"100","author":"Duan","year":"2018","journal-title":"Neuron"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/nri2685","article-title":"Post-transcriptional regulons coordinate the initiation and resolution of inflammation","volume":"10","author":"Anderson","year":"2010","journal-title":"Nat. Rev. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1038\/ni1584","article-title":"Post-transcriptional control of cytokine production","volume":"9","author":"Anderson","year":"2008","journal-title":"Nat. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1189\/jlb.1206754","article-title":"Chemokine and chemoattractant receptor expression: Post-transcriptional regulation","volume":"82","author":"Hamilton","year":"2007","journal-title":"J. Leukoc. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1038\/cdd.2014.112","article-title":"The complexity of miRNA-mediated repression","volume":"22","author":"Wilczynska","year":"2015","journal-title":"Cell Death Differ."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1101\/cshperspect.a032813","article-title":"Stress Granules and Processing Bodies in Translational Control","volume":"11","author":"Ivanov","year":"2019","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1172","DOI":"10.1093\/jnci\/djt184","article-title":"MHC Class I Antigen Processing and Presenting Machinery: Organization, Function, and Defects in Tumor Cells","volume":"105","author":"Leone","year":"2013","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1038\/ni.2048","article-title":"IFIT1 is an antiviral protein that recognizes 5\u2032-triphosphate RNA","volume":"12","author":"Pichlmair","year":"2011","journal-title":"Nat. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Busse, D.C., Habgood-Coote, D., Clare, S., Brandt, C., Bassano, I., Kaforou, M., Herberg, J., Levin, M., Eleouet, J.F., and Kellam, P. (2020). Interferon-Induced Protein 44 and Interferon-Induced Protein 44-Like Restrict Replication of Respiratory Syncytial Virus. J. Virol., 94.","DOI":"10.1128\/JVI.00297-20"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Daniels, B.P., Holman, D.W., Cruz-Orengo, L., Jujjavarapu, H., Durrant, D.M., and Klein, R.S. (2014). Viral Pathogen-Associated Molecular Patterns Regulate Blood-Brain Barrier Integrity via Competing Innate Cytokine Signals. Mbio, 5.","DOI":"10.1128\/mBio.01476-14"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Bian, P., Ye, C., Zheng, X., Luo, C., Yang, J., Li, M., Wang, Y., Yang, J., Zhou, Y., and Zhang, F. (2020). RIPK3 Promotes JEV Replication in Neurons via Downregulation of IFI44L. Front. Microbiol., 11.","DOI":"10.3389\/fmicb.2020.00368"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1038\/s41564-018-0244-1","article-title":"A CRISPR screen identifies IFI6 as an ER-resident interferon effector that blocks flavivirus replication","volume":"3","author":"Richardson","year":"2018","journal-title":"Nat. Microbiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.tim.2012.03.009","article-title":"Viral disruption of the blood brain barrier","volume":"20","author":"Spindler","year":"2012","journal-title":"Trends Microbiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1016\/j.immuni.2017.06.012","article-title":"Protective and Pathological Immunity during Central Nervous System Infections","volume":"46","author":"Klein","year":"2017","journal-title":"Immunity"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3308","DOI":"10.1016\/j.ajpath.2014.08.019","article-title":"Interferon-gamma Safeguards Blood-Brain Barrier during Experimental Autoimmune Encephalomyelitis","volume":"184","author":"Ni","year":"2014","journal-title":"Am. J. Pathol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Bonney, S., Seitz, S., Ryan, C.A., Jones, K.L., Clarke, P., Tyler, K.L., and Siegenthaler, J.A. (2019). Gamma Interferon Alters Junctional Integrity via Rho Kinase, Resulting in Blood-Brain Barrier Leakage in Experimental Viral Encephalitis. Mbio, 10.","DOI":"10.1128\/mBio.01675-19"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1172\/JCI88720","article-title":"Regional astrocyte IFN signaling restricts pathogenesis during neurotropic viral infection","volume":"127","author":"Daniels","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Daniels, B.P., and Klein, R.S. (2015). Knocking on Closed Doors: Host Interferons Dynamically Regulate Blood-Brain Barrier Function during Viral Infections of the Central Nervous System. PLoS Pathog., 11.","DOI":"10.1371\/journal.ppat.1005096"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1002\/sctm.18-0155","article-title":"Concise Review: The Endothelial Cell Extracellular Matrix Regulates Tissue Homeostasis and Repair","volume":"8","author":"Witjas","year":"2019","journal-title":"Stem Cells Transl. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1016\/j.yexcr.2007.01.024","article-title":"The impact of glia-derived extracellular matrices on the barrier function of cerebral endothelial cells: An in vitro study","volume":"313","author":"Hartmann","year":"2007","journal-title":"Exp. Cell Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1083\/jcb.111.2.757","article-title":"Characterization of the Activation of Latent Tgf-Beta by Cocultures of Endothelial-Cells and Pericytes or Smooth-Muscle Cells\u2014A Self-Regulating System","volume":"111","author":"Sato","year":"1990","journal-title":"J. Cell Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"4544","DOI":"10.1073\/pnas.86.12.4544","article-title":"An Activated Form of Transforming Growth Factor-Beta Is Produced by Cocultures of Endothelial-Cells and Pericytes","volume":"86","author":"Antonelliorlidge","year":"1989","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1002\/wdev.86","article-title":"The TGFbeta Superfamily Signaling Pathway","volume":"2","author":"Weiss","year":"2013","journal-title":"Wiley Interdiscip. Rev. Dev. Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1093\/jb\/mvs089","article-title":"Matrix control of transforming growth factor-beta function","volume":"152","author":"Horiguchi","year":"2012","journal-title":"J. Biochem."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Moon, S., Lee, S., Caesar, J.A., Pruchenko, S., Leask, A., Knowles, J.A., Sinon, J., and Chaqour, B. (2020). A CTGF-YAP Regulatory Pathway Is Essential for Angiogenesis and Barriergenesis in the Retina. Iscience, 23.","DOI":"10.1101\/2020.03.16.994293"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"36450","DOI":"10.1038\/srep36450","article-title":"The role of pericytic laminin in blood brain barrier integrity maintenance","volume":"6","author":"Gautam","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1242\/dev.01551","article-title":"Selective ablation of alpha v integrins in the central nervous system leads to cerebral hemorrhage, seizures, axonal degeneration and premature death","volume":"132","author":"McCarty","year":"2005","journal-title":"Development"},{"key":"ref_59","first-page":"2817","article-title":"Loss of the transcription factor RBPJ induces disease-promoting properties in brain pericytes","volume":"227","author":"Kato","year":"2019","journal-title":"Acta Physiol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"F1230","DOI":"10.1152\/ajprenal.00030.2016","article-title":"Maintenance of vascular integrity by pericytes is essential for normal kidney function","volume":"311","author":"Lemos","year":"2016","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/s40348-020-00105-5","article-title":"A role for the alpha-8 integrin chain (itga8) in glomerular homeostasis of the kidney","volume":"7","author":"Marek","year":"2020","journal-title":"Mol. Cell. Pediatrics"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.nbd.2012.01.008","article-title":"Fibroblast growth factors preserve blood-brain barrier integrity through RhoA inhibition after intracerebral hemorrhage in mice","volume":"46","author":"Huang","year":"2012","journal-title":"Neurobiol. Dis."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1111\/j.1471-4159.2004.02343.x","article-title":"A pericyte-derived angiopoietin-1 multimeric complex induces occludin gene expression in brain capillary endothelial cells through Tie-2 activation in vitro","volume":"89","author":"Hori","year":"2004","journal-title":"J. Neurochem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"L718","DOI":"10.1152\/ajplung.00014.2006","article-title":"Diverse effects of vascular endothelial growth factor on human pulmonary endothelial barrier and migration","volume":"291","author":"Mirzapoiazova","year":"2006","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_65","first-page":"501","article-title":"Vascular endothelial growth factor acts as a pericyte mitogen under hypoxic conditions","volume":"79","author":"Yamagishi","year":"1999","journal-title":"Lab. Investig."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"3709","DOI":"10.1182\/blood-2010-11-316752","article-title":"VEGF and FGF prime vascular tube morphogenesis and sprouting directed by hematopoietic stem cell cytokines","volume":"117","author":"Stratman","year":"2011","journal-title":"Blood"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.ydbio.2003.08.015","article-title":"Pericyte production of cell-associated VEGF is differentiation-dependent and is associated with endothelial survival","volume":"264","author":"Darland","year":"2003","journal-title":"Dev. Biol."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Rahimi, N. (2017). Defenders and Challengers of Endothelial Barrier Function. Front. Immunol., 8.","DOI":"10.3389\/fimmu.2017.01847"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Tratwal, J., Mathiasen, A.B., Juhl, M., Brorsen, S.K., Kastrup, J., and Ekblond, A. (2015). Influence of vascular endothelial growth factor stimulation and serum deprivation on gene activation patterns of human adipose tissue-derived stromal cells. Stem Cell Res. Ther., 6.","DOI":"10.1186\/s13287-015-0062-9"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1016\/j.bbagen.2005.12.020","article-title":"Galectin-3: An open-ended story","volume":"1760","author":"Dumic","year":"2006","journal-title":"Biochim. Biophys. Acta Gen. Subj."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"3580","DOI":"10.1091\/mbc.e04-03-0236","article-title":"NG2 proteoglycan promotes endothelial cell motility and angiogenesis via engagement of galectin-3 and alpha 3 beta 1 integrin","volume":"15","author":"Fukushi","year":"2004","journal-title":"Mol. Biol. Cell"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1007\/s00401-018-1893-0","article-title":"Targeting pericytes for therapeutic approaches to neurological disorders","volume":"136","author":"Cheng","year":"2018","journal-title":"Acta Neuropathol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1177\/0271678X15616138","article-title":"Ion channel networks in the control of cerebral blood flow","volume":"36","author":"Longden","year":"2016","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Hariharan, A., Weir, N., Robertson, C., He, L., Betsholtz, C., and Longden, T.A. (2020). The Ion Channel and GPCR Toolkit of Brain Capillary Pericytes. Front. Cell. Neurosci., 14.","DOI":"10.3389\/fncel.2020.601324"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.ajps.2019.09.002","article-title":"The solute carrier transporters and the brain: Physiological and pharmacological implications","volume":"15","author":"Hu","year":"2020","journal-title":"Asian J. Pharm. Sci."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"11186","DOI":"10.1038\/s41598-020-68019-w","article-title":"Prostaglandin E2 breaks down pericyte-endothelial cell interaction via EP1 and EP4-dependent downregulation of pericyte N-cadherin, connexin-43, and R-Ras","volume":"10","author":"Perrot","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1038\/jcbfm.2012.45","article-title":"Deletion of astroglial connexins weakens the blood-brain barrier","volume":"32","author":"Ezan","year":"2012","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"7580","DOI":"10.1523\/JNEUROSCI.0187-17.2017","article-title":"Vascular Pericyte Impairment and Connexin43 Gap Junction Deficit Contribute to Vasomotor Decline in Diabetic Retinopathy","volume":"37","author":"Ivanova","year":"2017","journal-title":"J. Neurosci."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1161\/01.RES.0000091259.84556.D5","article-title":"Gap junction communication mediates transforming growth factor-beta activation and endothelial-induced mural cell differentiation","volume":"93","author":"Hirschi","year":"2003","journal-title":"Circ. Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"3591","DOI":"10.1073\/pnas.1218498110","article-title":"Inhibition of the prostaglandin receptor EP2 following status epilepticus reduces delayed mortality and brain inflammation","volume":"110","author":"Jiang","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/jb\/mvr068","article-title":"Ectodomain shedding and remnant peptide signalling of EGFRs and their ligands","volume":"150","author":"Higashiyama","year":"2011","journal-title":"J. Biochem."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/0026-2862(92)90085-4","article-title":"Epidermal Growth-Factor Receptor at Endothelial-Cell and Pericyte Interdigitation in Human Granulation-Tissue","volume":"44","author":"Shin","year":"1992","journal-title":"Microvasc. Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1016\/j.ajpath.2010.12.031","article-title":"Novel Protective Properties of IGFBP-3 Result in Enhanced Pericyte Ensheathment, Reduced Microglial Activation, Increased Microglial Apoptosis, and Neuronal Protection after Ischemic Retinal Injury","volume":"178","author":"Kielczewski","year":"2011","journal-title":"Am. J. Pathol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1161\/CIRCRESAHA.109.199059","article-title":"Insulin-Like Growth Factor Binding Protein-3 Mediates Vascular Repair by Enhancing Nitric Oxide Generation","volume":"105","author":"Kielczewski","year":"2009","journal-title":"Circ. Res."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"10589","DOI":"10.1073\/pnas.0702031104","article-title":"IGFBP3 suppresses retinopathy through suppression of oxygen-induced vessel loss and promotion of vascular regrowth","volume":"104","author":"Lofqvist","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"5376","DOI":"10.1167\/iovs.13-12497","article-title":"IGFBP-3 and TNF-alpha Regulate Retinal Endothelial Cell Apoptosis","volume":"54","author":"Zhang","year":"2013","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1038\/hr.2010.201","article-title":"Reactive oxygen species and vascular biology: Implications in human hypertension","volume":"34","author":"Touyz","year":"2011","journal-title":"Hypertens. Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1111\/jnc.13607","article-title":"Neuroinflammation: The devil is in the details","volume":"139","author":"DiSabato","year":"2016","journal-title":"J. Neurochem."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1002\/glia.22930","article-title":"Sequential Activation of Microglia and Astrocyte Cytokine Expression Precedes Increased Iba-1 or GFAP Immunoreactivity Following Systemic Immune Challenge","volume":"64","author":"Norden","year":"2016","journal-title":"Glia"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1038\/s41590-020-00840-x","article-title":"Untuned antiviral immunity in COVID-19 revealed by temporal type I\/III interferon patterns and flu comparison","volume":"22","author":"Galani","year":"2021","journal-title":"Nat. Immunol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1777","DOI":"10.1007\/s00134-020-06147-7","article-title":"Pericyte alteration sheds light on micro-vasculopathy in COVID-19 infection","volume":"46","author":"Hubiche","year":"2020","journal-title":"Intensive Care Med."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/7\/1784\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:30:44Z","timestamp":1760164244000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/7\/1784"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,14]]},"references-count":91,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2021,7]]}},"alternative-id":["cells10071784"],"URL":"https:\/\/doi.org\/10.3390\/cells10071784","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,14]]}}}