Retinal endothelial cell phenotypic modifications during experimental autoimmune uveitis: a transcriptomic approach.
Blood-retinal barrier
Endothelial cells
Inflammation
Lipocalin 2
RNA-Seq
Transcriptome
Uveitis
ackr1
lrg1
serpina3n
Journal
BMC ophthalmology
ISSN: 1471-2415
Titre abrégé: BMC Ophthalmol
Pays: England
ID NLM: 100967802
Informations de publication
Date de publication:
17 Mar 2020
17 Mar 2020
Historique:
received:
06
08
2019
accepted:
03
02
2020
entrez:
19
3
2020
pubmed:
19
3
2020
medline:
29
1
2021
Statut:
epublish
Résumé
Blood-retinal barrier cells are known to exhibit a massive phenotypic change during experimental autoimmune uveitis (EAU) development. In an attempt to investigate the mechanisms of blood-retinal barrier (BRB) breakdown at a global level, we studied the gene regulation of total retinal cells and retinal endothelial cells during non-infectious uveitis. Retinal endothelial cells were isolated by flow cytometry either in Tie2-GFP mice (CD31 Retinal endothelial cell sorting in wild type C57BL/6 mice was validated by comparative transcriptome analysis with retinal endothelial cells sorted from Tie2-GFP mice, which express GFP under the control of the endothelial-specific receptor tyrosine kinase promoter Tie2. RNA-Seq analysis of total retinal cells mainly brought to light upregulation of genes involved in antigen presentation and T cell activation during EAU. Specific transcriptome analysis of retinal endothelial cells allowed us to identify 82 genes modulated in retinal endothelial cells during EAU development. Protein expression of 5 of those genes (serpina3n, lcn2, ackr1, lrg1 and lamc3) was validated at the level of inner BRB cells. Those data not only confirm the involvement of known pathogenic molecules but further provide a list of new candidate genes and pathways possibly implicated in inner BRB breakdown during non-infectious posterior uveitis.
Sections du résumé
BACKGROUND
BACKGROUND
Blood-retinal barrier cells are known to exhibit a massive phenotypic change during experimental autoimmune uveitis (EAU) development. In an attempt to investigate the mechanisms of blood-retinal barrier (BRB) breakdown at a global level, we studied the gene regulation of total retinal cells and retinal endothelial cells during non-infectious uveitis.
METHODS
METHODS
Retinal endothelial cells were isolated by flow cytometry either in Tie2-GFP mice (CD31
RESULTS
RESULTS
Retinal endothelial cell sorting in wild type C57BL/6 mice was validated by comparative transcriptome analysis with retinal endothelial cells sorted from Tie2-GFP mice, which express GFP under the control of the endothelial-specific receptor tyrosine kinase promoter Tie2. RNA-Seq analysis of total retinal cells mainly brought to light upregulation of genes involved in antigen presentation and T cell activation during EAU. Specific transcriptome analysis of retinal endothelial cells allowed us to identify 82 genes modulated in retinal endothelial cells during EAU development. Protein expression of 5 of those genes (serpina3n, lcn2, ackr1, lrg1 and lamc3) was validated at the level of inner BRB cells.
CONCLUSION
CONCLUSIONS
Those data not only confirm the involvement of known pathogenic molecules but further provide a list of new candidate genes and pathways possibly implicated in inner BRB breakdown during non-infectious posterior uveitis.
Identifiants
pubmed: 32183784
doi: 10.1186/s12886-020-1333-5
pii: 10.1186/s12886-020-1333-5
pmc: PMC7076950
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
106Subventions
Organisme : Fonds Voor Research In Oftalmologie
ID : None
Organisme : Fonds d'encouragement à la recherche
ID : NA
Commentaires et corrections
Type : ErratumIn
Références
Daneman R, Zhou L, Agalliu D, Cahoy JD, Kaushal A, Barres BA. The mouse blood-brain barrier transcriptome: a new resource for understanding the development and function of brain endothelial cells. PLoS One. 2010;5(10):e13741.
pubmed: 21060791
pmcid: 2966423
doi: 10.1371/journal.pone.0013741
pubmeddev, RR C. Understanding autoimmune uveitis through animal models. The Friedenwald Lecture. - PubMed - NCBI [Internet]. [cited 2019 Nov 25]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/21450922 .
Dewispelaere R, Lipski D, Foucart V, Bruyns C, Frère A, Caspers L, et al. ICAM-1 and VCAM-1 are differentially expressed on blood-retinal barrier cells during experimental autoimmune uveitis. Exp Eye Res. 2015;137:94–102.
pubmed: 26093277
doi: 10.1016/j.exer.2015.06.017
Makhoul M, Dewispelaere R, Relvas LJ, Elmaleh V, Caspers L, Bruyns C, et al. Characterization of retinal expression of vascular cell adhesion molecule (VCAM-1) during experimental autoimmune uveitis. Exp Eye Res. 2012;101:27–35.
pubmed: 22749846
doi: 10.1016/j.exer.2012.05.012
Xu H, Dawson R, Crane IJ, Liversidge J. Leukocyte diapedesis in vivo induces transient loss of tight junction protein at the blood-retina barrier. Invest Ophthalmol Vis Sci. 2005;46(7):2487–94.
pubmed: 15980240
doi: 10.1167/iovs.04-1333
Zhao S, Li T, Li J, Lu Q, Han C, Wang N, et al. miR-23b-3p induces the cellular metabolic memory of high glucose in diabetic retinopathy through a SIRT1-dependent signalling pathway. Diabetologia. 2016;59(3):644–54.
pubmed: 26687158
doi: 10.1007/s00125-015-3832-0
Savage SR, Bretz CA, Penn JS. RNA-Seq reveals a role for NFAT-signaling in human retinal microvascular endothelial cells treated with TNFα. PLoS One. 2015;10(1):e0116941.
pubmed: 25617622
pmcid: 4305319
doi: 10.1371/journal.pone.0116941
Wang X, Abraham S, McKenzie JAG, Jeffs N, Swire M, Tripathi VB, et al. LRG1 promotes angiogenesis by modulating endothelial TGF-β signalling. Nature. 2013;499(7458):306–11.
pubmed: 23868260
doi: 10.1038/nature12345
Kusuhara S, Fukushima Y, Fukuhara S, Jakt LM, Okada M, Shimizu Y, et al. Arhgef15 promotes retinal angiogenesis by mediating VEGF-induced Cdc42 activation and potentiating RhoJ inactivation in endothelial cells. PLoS One. 2012;7(9):e45858.
pubmed: 23029280
pmcid: 3448698
doi: 10.1371/journal.pone.0045858
Steinle JJ, Zhang Q, Thompson KE, Toutounchian J, Yates CR, Soderland C, et al. Intra-ophthalmic artery chemotherapy triggers vascular toxicity through endothelial cell inflammation and leukostasis. Invest Ophthalmol Vis Sci. 2012;53(4):2439–45.
pubmed: 22427570
pmcid: 3995559
doi: 10.1167/iovs.12-9466
Takase H, Matsumoto K, Yamadera R, Kubota Y, Otsu A, Suzuki R, et al. Genome-wide identification of endothelial cell-enriched genes in the mouse embryo. Blood. 2012;120(4):914–23.
pubmed: 22535667
doi: 10.1182/blood-2011-12-398156
Browning AC, Halligan EP, Stewart EA, Swan DC, Dove R, Samaranayake GJ, et al. Comparative gene expression profiling of human umbilical vein endothelial cells and ocular vascular endothelial cells. Br J Ophthalmol. 2012;96(1):128–32.
pubmed: 22028475
doi: 10.1136/bjophthalmol-2011-300572
Strasser GA, Kaminker JS, Tessier-Lavigne M. Microarray analysis of retinal endothelial tip cells identifies CXCR4 as a mediator of tip cell morphology and branching. Blood. 2010;115(24):5102–10.
pubmed: 20154215
doi: 10.1182/blood-2009-07-230284
Abukawa H, Tomi M, Kiyokawa J, Hori S, Kondo T, Terasaki T, et al. Modulation of retinal capillary endothelial cells by Müller glial cell-derived factors. Mol Vis. 2009;15:451–7.
pubmed: 19247458
pmcid: 2647974
Smith JR, Choi D, Chipps TJ, Pan Y, Zamora DO, Davies MH, et al. Unique gene expression profiles of donor-matched human retinal and choroidal vascular endothelial cells. Invest Ophthalmol Vis Sci. 2007;48(6):2676–84.
pubmed: 17525199
doi: 10.1167/iovs.06-0598
Ohtsuki S, Tomi M, Hata T, Nagai Y, Hori S, Mori S, et al. Dominant expression of androgen receptors and their functional regulation of organic anion transporter 3 in rat brain capillary endothelial cells; comparison of gene expression between the blood-brain and -retinal barriers. J Cell Physiol. 2005;204(3):896–900.
pubmed: 15795901
doi: 10.1002/jcp.20352
Silverman MD, Babra B, Pan Y, Planck SR, Rosenbaum JT. Differential E-selectin expression by iris versus retina microvascular endothelial cells cultured from the same individuals. Microvasc Res. 2005;70(1):32–42.
pubmed: 16087199
doi: 10.1016/j.mvr.2005.07.001
Knight BC, Brunton CL, Modi NC, Wallace GR, Stanford MR. The effect of Toxoplasma gondii infection on expression of chemokines by rat retinal vascular endothelial cells. J Neuroimmunol. 2005;160(1):41–7.
pubmed: 15710456
doi: 10.1016/j.jneuroim.2004.10.023
Bharadwaj AS, Appukuttan B, Wilmarth PA, Pan Y, Stempel AJ, Chipps TJ, et al. Role of the Retinal Vascular Endothelial Cell in Ocular Disease. Prog Retin Eye Res. 2013;32:102–80.
pubmed: 22982179
doi: 10.1016/j.preteyeres.2012.08.004
Silverman MD, Zamora DO, Pan Y, Texeira PV, Baek S-H, Planck SR, et al. Constitutive and inflammatory mediator-regulated fractalkine expression in human ocular tissues and cultured cells. Invest Ophthalmol Vis Sci. 2003;44(4):1608–15.
pubmed: 12657599
doi: 10.1167/iovs.02-0233
Klaassen I, Van Noorden CJF, Schlingemann RO. Molecular basis of the inner blood-retinal barrier and its breakdown in diabetic macular edema and other pathological conditions. Prog Retin Eye Res. 2013;34:19–48.
pubmed: 23416119
doi: 10.1016/j.preteyeres.2013.02.001
Shao H, Liao T, Ke Y, Shi H, Kaplan HJ, Sun D. Severe chronic experimental autoimmune uveitis (EAU) of the C57BL/6 mouse induced by adoptive transfer of IRBP1-20-specific T cells. Exp Eye Res. 2006;82(2):323–31.
pubmed: 16125173
doi: 10.1016/j.exer.2005.07.008
Xu H, Koch P, Chen M, Lau A, Reid DM, Forrester JV. A clinical grading system for retinal inflammation in the chronic model of experimental autoimmune uveoretinitis using digital fundus images. Exp Eye Res. 2008;87(4):319–26.
pubmed: 18634784
doi: 10.1016/j.exer.2008.06.012
Tachikawa M, Toki H, Tomi M, Hosoya K. Gene expression profiles of ATP-binding cassette transporter A and C subfamilies in mouse retinal vascular endothelial cells. Microvasc Res. 2008;75(1):68–72.
pubmed: 17574281
doi: 10.1016/j.mvr.2007.05.002
Liao Y, Smyth GK, Shi W. featureCounts: an efficient general purpose program for assigning sequence reads to genomic features. Bioinforma Oxf Engl. 2014;30(7):923–30.
doi: 10.1093/bioinformatics/btt656
Dennis G, Sherman BT, Hosack DA, Yang J, Gao W, Lane HC, et al. DAVID: Database for Annotation, Visualization, and Integrated Discovery. Genome Biol. 2003;4(5):P3.
pubmed: 12734009
doi: 10.1186/gb-2003-4-5-p3
Constien R, Forde A, Liliensiek B, Gröne H-J, Nawroth P, Hämmerling G, et al. Characterization of a novel EGFP reporter mouse to monitor Cre recombination as demonstrated by a Tie2 Cre mouse line. Genesis. 2001;30(1):36–44.
pubmed: 11353516
doi: 10.1002/gene.1030
Darrow AL, Maresh JG, Shohet RV. Mouse models and techniques for the isolation of the diabetic endothelium. ISRN Endocrinol. 2013;2013:165397.
pubmed: 23840960
pmcid: 3693106
doi: 10.1155/2013/165397
Lipski DA, Dewispelaere R, Foucart V, Caspers LE, Defrance M, Bruyns C, et al. MHC class II expression and potential antigen-presenting cells in the retina during experimental autoimmune uveitis. J Neuroinflammation. 2017;14(1):136.
pubmed: 28720143
pmcid: 5516361
doi: 10.1186/s12974-017-0915-5
Yang Y, Xiao X, Li F, Du L, Kijlstra A, Yang P. Increased IL-7 expression in Vogt-Koyanagi-Harada disease. Invest Ophthalmol Vis Sci. 2012;53(2):1012–7.
pubmed: 22247488
doi: 10.1167/iovs.11-8505
Sampson JF, Hasegawa E, Mulki L, Suryawanshi A, Jiang S, Chen W-S, et al. Galectin-8 Ameliorates Murine Autoimmune Ocular Pathology and Promotes a Regulatory T Cell Response. PLoS One. 2015;10(6):e0130772.
pubmed: 26126176
pmcid: 4488339
doi: 10.1371/journal.pone.0130772
Wisniewska-Kruk J, Hoeben KA, Vogels IMC, Gaillard PJ, Van Noorden CJF, Schlingemann RO, et al. A novel co-culture model of the blood-retinal barrier based on primary retinal endothelial cells, pericytes and astrocytes. Exp Eye Res. 2012;96(1):181–90.
pubmed: 22200486
doi: 10.1016/j.exer.2011.12.003
Motoike T, Loughna S, Perens E, Roman BL, Liao W, Chau TC, et al. Universal GFP reporter for the study of vascular development. Genes. 2000;28(2):75–81.
doi: 10.1002/1526-968X(200010)28:2<75::AID-GENE50>3.0.CO;2-S
Su X, Sorenson CM, Sheibani N. Isolation and characterization of murine retinal endothelial cells. Mol Vis. 2003;9:171–8.
pubmed: 12740568
Marelli-Berg FM, Clement M, Mauro C, Caligiuri G. An immunologist’s guide to CD31 function in T-cells. J Cell Sci. 2013;126(11):2343–52.
pubmed: 23761922
doi: 10.1242/jcs.124099
Aristorena M, Blanco FJ, de Casas-Engel ML, Ojeda-Fernandez L, Gallardo-Vara E, Corbi A, et al. Expression of endoglin isoforms in the myeloid lineage and their role during aging and macrophage polarization. J Cell Sci. 2014;127(12):2723–35.
pubmed: 24777481
Matsusaka T. Tridimensional views of the relationship of pericytes to endothelial cells of capillaries in the human choroid and retina. J Electron Microsc. 1975;24(1):13–8.
Armulik A, Genové G, Betsholtz C. Pericytes: developmental, physiological, and pathological perspectives, problems, and promises. Dev Cell. 2011;21(2):193–215.
pubmed: 21839917
doi: 10.1016/j.devcel.2011.07.001
Daneman R, Zhou L, Kebede AA, Barres BA. Pericytes are required for blood-brain barrier integrity during embryogenesis. Nature. 2010;468(7323):562–6.
pubmed: 20944625
pmcid: 3241506
doi: 10.1038/nature09513
Whitmore SS, Wagner AH, DeLuca AP, Drack AV, Stone EM, Tucker BA, et al. Transcriptomic analysis across nasal, temporal, and macular regions of human neural retina and RPE/choroid by RNA-Seq. Exp Eye Res. 2014;129:93–106.
pubmed: 25446321
pmcid: 4259842
doi: 10.1016/j.exer.2014.11.001
Siegert S, Cabuy E, Scherf BG, Kohler H, Panda S, Le Y-Z, et al. Transcriptional code and disease map for adult retinal cell types. Nat Neurosci. 2012;15(3):487–95.
pubmed: 22267162
doi: 10.1038/nn.3032
McKenzie JAG, Fruttiger M, Abraham S, Lange CAK, Stone J, Gandhi P, et al. Apelin Is Required for Non-Neovascular Remodeling in the Retina. Am J Pathol. 2012;180(1):399–409.
pubmed: 22067912
pmcid: 3244602
doi: 10.1016/j.ajpath.2011.09.035
Xu H, Forrester JV, Liversidge J, Crane IJ. Leukocyte trafficking in experimental autoimmune uveitis: breakdown of blood-retinal barrier and upregulation of cellular adhesion molecules. Invest Ophthalmol Vis Sci. 2003;44(1):226–34.
pubmed: 12506079
doi: 10.1167/iovs.01-1202
Xu H, Manivannan A, Liversidge J, Sharp PF, Forrester JV, Crane IJ. Involvement of CD44 in leukocyte trafficking at the blood-retinal barrier. J Leukoc Biol. 2002;72(6):1133–41.
pubmed: 12488494
doi: 10.1189/jlb.72.6.1133
Çerçi P, Altıner S, İnal A, Köse K, Keskin G, Ölmez Ü. Investigating the role of IL-33 in the pathogenesis of Behçet’s Disease. Acta Clin Belg. 2017;17:1–5.
Dick AD. Doyne lecture 2016: intraocular health and the many faces of inflammation. Eye Lond Engl. 2017;31(1):87–96.
Salom D, Sanz-Marco E, Mullor JL, Lopez-Prats MJ, Garcia-Delpech S, Udaondo P, et al. Aqueous humor neutrophil gelatinase-associated lipocalin levels in patients with idiopathic acute anterior uveitis. Mol Vis. 2010;16:1448–52.
pubmed: 20680102
pmcid: 2913142
Serada S, Fujimoto M, Ogata A, Terabe F, Hirano T, Iijima H, et al. iTRAQ-based proteomic identification of leucine-rich alpha-2 glycoprotein as a novel inflammatory biomarker in autoimmune diseases. Ann Rheum Dis. 2010;69(4):770–4.
pubmed: 19854709
doi: 10.1136/ard.2009.118919
Minten C, Alt C, Gentner M, Frei E, Deutsch U, Lyck R, et al. DARC shuttles inflammatory chemokines across the blood-brain barrier during autoimmune central nervous system inflammation. Brain J Neurol. 2014;137(Pt 5):1454–69.
doi: 10.1093/brain/awu045
Petković F, Živanović J, Blaževski J, Timotijević G, Momčilović M, Stanojević Ž, et al. Activity, but not mRNA expression of gelatinases correlates with susceptibility to experimental autoimmune encephalomyelitis. Neuroscience. 2015;292:1–12.
pubmed: 25701126
doi: 10.1016/j.neuroscience.2015.02.015
Zhang C, Nie J, Feng L, Luo W, Yao J, Wang F, et al. The Emerging Roles of Clusterin in Reduction of Both Blood Retina Barrier Breakdown and Neural Retina Damage in Diabetic Retinopathy. Discov Med. 2016;21(116):227–37.
pubmed: 27232509
Groeger G, Doonan F, Cotter TG, Donovan M. Reactive oxygen species regulate prosurvival ERK1/2 signaling and bFGF expression in gliosis within the retina. Invest Ophthalmol Vis Sci. 2012;53(10):6645–54.
pubmed: 22956616
doi: 10.1167/iovs.12-10525
Read RW, Szalai AJ, Vogt SD, McGwin G, Barnum SR. Genetic deficiency of C3 as well as CNS-targeted expression of the complement inhibitor sCrry ameliorates experimental autoimmune uveoretinitis. Exp Eye Res. 2006;82(3):389–94.
pubmed: 16143328
doi: 10.1016/j.exer.2005.07.011
Copland DA, Hussain K, Baalasubramanian S, Hughes TR, Morgan BP, Xu H, et al. Systemic and local anti-C5 therapy reduces the disease severity in experimental autoimmune uveoretinitis. Clin Exp Immunol. 2010;159(3):303–14.
pubmed: 20002447
pmcid: 2819496
doi: 10.1111/j.1365-2249.2009.04070.x
Zhang L, Bell BA, Yu M, Chan C-C, Peachey NS, Fung J, et al. Complement anaphylatoxin receptors C3aR and C5aR are required in the pathogenesis of experimental autoimmune uveitis. J Leukoc Biol. 2016;99(3):447–54.
pubmed: 26394814
doi: 10.1189/jlb.3A0415-157R
Alt C, Duvefelt K, Franzén B, Yang Y, Engelhardt B. Gene and protein expression profiling of the microvascular compartment in experimental autoimmune encephalomyelitis in C57Bl/6 and SJL mice. Brain Pathol Zurich Switz. 2005;15(1):1–16.
Masciantonio MG, Lee CKS, Arpino V, Mehta S, Gill SE. The Balance Between Metalloproteinases and TIMPs: Critical Regulator of Microvascular Endothelial Cell Function in Health and Disease. Prog Mol Biol Transl Sci. 2017;147:101–31.
pubmed: 28413026
doi: 10.1016/bs.pmbts.2017.01.001
El-Shabrawi YG, Christen WG, Foster SC. Correlation of metalloproteinase-2 and -9 with proinflammatory cytokines interleukin-1b, interleukin-12 and the interleukin-1 receptor antagonist in patients with chronic uveitis. Curr Eye Res. 2000;20(3):211–4.
pubmed: 10694897
doi: 10.1076/0271-3683(200003)2031-9FT211
Di Girolamo N, Verma MJ, McCluskey PJ, Lloyd A, Wakefield D. Increased matrix metalloproteinases in the aqueous humor of patients and experimental animals with uveitis. Curr Eye Res. 1996;15(10):1060–8.
pubmed: 8921246
doi: 10.3109/02713689609017656
El-Shabrawi Y, Walch A, Hermann J, Egger G, Foster CS. Inhibition of MMP-dependent chemotaxis and amelioration of experimental autoimmune uveitis with a selective metalloproteinase-2 and -9 inhibitor. J Neuroimmunol. 2004;155(1–2):13–20.
pubmed: 15342192
doi: 10.1016/j.jneuroim.2004.05.010
Vinores SA, Chan CC, Vinores MA, Matteson DM, Chen YS, Klein DA, et al. Increased vascular endothelial growth factor (VEGF) and transforming growth factor beta (TGFbeta) in experimental autoimmune uveoretinitis: upregulation of VEGF without neovascularization. J Neuroimmunol. 1998;89(1–2):43–50.
pubmed: 9726824
doi: 10.1016/S0165-5728(98)00075-7
van Beijnum JR, Buurman WA, Griffioen AW. Convergence and amplification of toll-like receptor (TLR) and receptor for advanced glycation end products (RAGE) signaling pathways via high mobility group B1 (HMGB1). Angiogenesis. 2008;11(1):91–9.
pubmed: 18264787
doi: 10.1007/s10456-008-9093-5
Wykoff CC. Impact of intravitreal pharmacotherapies including antivascular endothelial growth factor and corticosteroid agents on diabetic retinopathy. Curr Opin Ophthalmol. 2017;28(3):213–8.
pubmed: 28376510
doi: 10.1097/ICU.0000000000000364
Tempest-Roe S, Joshi L, Dick AD, Taylor SRJ. Local therapies for inflammatory eye disease in translation: past, present and future. BMC Ophthalmol. 2013;13(1):39.
pubmed: 23914773
pmcid: 3750406
doi: 10.1186/1471-2415-13-39
Takamiya A, Takeda M, Yoshida A, Kiyama H. Expression of serine protease inhibitor 3 in ocular tissues in endotoxin-induced uveitis in rat. Invest Ophthalmol Vis Sci. 2001;42(11):2427–33.
pubmed: 11581179
Haile Y, Carmine-Simmen K, Olechowski C, Kerr B, Bleackley RC, Giuliani F. Granzyme B-inhibitor serpina3n induces neuroprotection in vitro and in vivo. J Neuroinflammation. 2015;12:157.
pubmed: 26337722
pmcid: 4558826
doi: 10.1186/s12974-015-0376-7
Munji RN, Soung AL, Weiner GA, Sohet F, Semple BD, Trivedi A, et al. Profiling the mouse brain endothelial transcriptome in health and disease models reveals a core blood-brain barrier dysfunction module. Nat Neurosci. 2019;22(11):1892–902.
pubmed: 31611708
pmcid: 6858546
doi: 10.1038/s41593-019-0497-x
Parmar T, Parmar VM, Arai E, Sahu B, Perusek L, Maeda A. Acute Stress Responses Are Early Molecular Events of Retinal Degeneration in Abca4-/-Rdh8-/- Mice After Light Exposure. Invest Ophthalmol Vis Sci. 2016;57(7):3257–67.
pubmed: 27315541
pmcid: 4928696
doi: 10.1167/iovs.15-18993
Rattner A, Nathans J. The Genomic Response to Retinal Disease and Injury: Evidence for Endothelin Signaling from Photoreceptors to Glia. J Neurosci. 2005;25(18):4540–9.
pubmed: 15872101
pmcid: 6725023
doi: 10.1523/JNEUROSCI.0492-05.2005
Nam Y, Kim J-H, Seo M, Kim J-H, Jin M, Jeon S, et al. Lipocalin-2 protein deficiency ameliorates experimental autoimmune encephalomyelitis: the pathogenic role of lipocalin-2 in the central nervous system and peripheral lymphoid tissues. J Biol Chem. 2014;289(24):16773–89.
pubmed: 24808182
pmcid: 4059121
doi: 10.1074/jbc.M113.542282
Berard JL, Zarruk JG, Arbour N, Prat A, Yong VW, Jacques FH, et al. Lipocalin 2 is a novel immune mediator of experimental autoimmune encephalomyelitis pathogenesis and is modulated in multiple sclerosis. Glia. 2012;60(7):1145–59.
pubmed: 22499213
doi: 10.1002/glia.22342
Hofmaier F, Hauck SM, Amann B, Degroote RL, Deeg CA. Changes in Matrix Metalloproteinase Network in a Spontaneous Autoimmune Uveitis Model. Invest Ophthalmol Vis Sci. 2011;52(5):2314–20.
pubmed: 21228380
doi: 10.1167/iovs.10-6475
Gul FC, Cicek D, Kaman D, Demir B, Nazik H. Changes of serum lipocalin-2 and retinol binding protein-4 levels in patients with psoriasis and Behçet’s disease. Eur J Dermatol. 2015;25(2):195–7.
pubmed: 25547333
doi: 10.1684/ejd.2014.2490
Salvi V, Sozio F, Sozzani S, Del Prete A. Role of Atypical Chemokine Receptors in Microglial Activation and Polarization. Front Aging Neurosci. 2017;9:148.
pubmed: 28603493
pmcid: 5445112
doi: 10.3389/fnagi.2017.00148
Thiriot A, Perdomo C, Cheng G, Novitzky-Basso I, McArdle S, Kishimoto JK, et al. Differential DARC/ACKR1 expression distinguishes venular from non-venular endothelial cells in murine tissues. BMC Biol. 2017;15(1).
Miyajima M, Nakajima M, Motoi Y, Moriya M, Sugano H, Ogino I, et al. Leucine-Rich α2-Glycoprotein Is a Novel Biomarker of Neurodegenerative Disease in Human Cerebrospinal Fluid and Causes Neurodegeneration in Mouse Cerebral Cortex. PLoS One. 2013;8(9):e74453.
pubmed: 24058569
pmcid: 3776841
doi: 10.1371/journal.pone.0074453
Shirai R, Hirano F, Ohkura N, Ikeda K, Inoue S. Up-regulation of the expression of leucine-rich alpha(2)-glycoprotein in hepatocytes by the mediators of acute-phase response. Biochem Biophys Res Commun. 2009;382(4):776–9.
pubmed: 19324010
pmcid: 7092932
doi: 10.1016/j.bbrc.2009.03.104
Fujimoto M, Serada S, Suzuki K, Nishikawa A, Ogata A, Nanki T, et al. Leucine-rich α2 -glycoprotein as a potential biomarker for joint inflammation during anti-interleukin-6 biologic therapy in rheumatoid arthritis. Arthritis Rheumatol Hoboken NJ. 2015;67(8):2056–60.
doi: 10.1002/art.39164
Serada S, Fujimoto M, Terabe F, Iijima H, Shinzaki S, Matsuzaki S, et al. Serum leucine-rich alpha-2 glycoprotein is a disease activity biomarker in ulcerative colitis. Inflamm Bowel Dis. 2012;18(11):2169–79.
pubmed: 22374925
doi: 10.1002/ibd.22936
Knockdown of Laminin gamma-3 (Lamc3) impairs motoneuron guidance in the zebrafish embryo. - PubMed - NCBI [Internet]. [cited 2019 Mar 30]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/?term=Knockdown+of+Laminin+gamma-3+(Lamc3)+impairs+motoneuron+guidance+in+the+zebrafish+embryo .
Kumar Vr S, Darisipudi MN, Steiger S, Devarapu SK, Tato M, Kukarni OP, et al. Cathepsin S Cleavage of Protease-Activated Receptor-2 on Endothelial Cells Promotes Microvascular Diabetes Complications. J Am Soc Nephrol JASN. 2016;27(6):1635–49.
pubmed: 26567242
doi: 10.1681/ASN.2015020208
Edgar R, Domrachev M, Lash AE. Gene Expression Omnibus: NCBI gene expression and hybridization array data repository. Nucleic Acids Res. 2002;30(1):207–10.
pubmed: 11752295
pmcid: 99122
doi: 10.1093/nar/30.1.207