Circular RNA DLGAP4 ameliorates ischemic stroke outcomes by targeting miR-143 to regulate endothelial-mesenchymal transition associated with blood–brain barrier integrity

Journal of Neuroscience

Volumn 38, Issue 1, 2018, Pages 32-50

  Bai, Ying ^a   Zhang, Yuan ^a   Han, Bing ^a   Yang, Li ^a   Chen, Xufeng ^b   Huang, Rongrong ^a   Wu, Fangfang ^a   Chao, Jie ^a   Liu, Pei ^c   Hu, Gang ^d   Zhang, John H ^e   Yao, Honghong ^a,c  

^a MEDICAL SCHOOL OF SOUTHEAST UNIVERSITY   (China)

^b THE FIRST AFFILIATED HOSPITAL OF NANJING MEDICAL UNIVERSITY   (China)

^c SOUTHEAST UNIVERSITY   (China)

^d NANJING MEDICAL UNIVERSITY   (China)

^e LOMA LINDA UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Blood; Brain barrier integrity; Circular RNA DLGAP4; Endothelial mesenchymal transition; Ischemic stroke; MiR 143; Transient middle cerebral artery occlusion

Indexed keywords

CIRCULAR RNA DLGAP4; CLAUDIN 5; COLLAGEN TYPE 1; COLLAGEN TYPE 3; MICRORNA 143; OCCLUDIN; PROTEIN ZO1; RNA; TIGHT JUNCTION PROTEIN; UBIQUITIN PROTEIN LIGASE E3; UNCLASSIFIED DRUG; DISKS LARGE HOMOLOG 4; DLG4 PROTEIN, MOUSE; HECTD1 PROTEIN, MOUSE; MICRORNA; MIRN143 MICRORNA, MOUSE; RNA, CIRCULAR; UBIQUITIN PROTEIN LIGASE;

AGED; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BLOOD BRAIN BARRIER; BRAIN BLOOD FLOW; BRAIN INFARCTION; BRAIN INFARCTION SIZE; BRAIN ISCHEMIA; CLINICAL ARTICLE; CONTROLLED STUDY; EPITHELIAL MESENCHYMAL TRANSITION; FEMALE; FLUORESCENCE IN SITU HYBRIDIZATION; GENE TARGETING; HUMAN; HUMAN CELL; IMMUNOFLUORESCENCE; LUCIFERASE ASSAY; MALE; MEMBRANE DAMAGE; MIDDLE CEREBRAL ARTERY OCCLUSION; MOUSE; NONHUMAN; NORTHERN BLOTTING; NUCLEAR MAGNETIC RESONANCE IMAGING; NUTRITIONAL DEFICIENCY; OXYGEN GLUCOSE DEPRIVATION; PRIORITY JOURNAL; PROTEIN EXPRESSION; REAL TIME POLYMERASE CHAIN REACTION; REOXYGENATION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; UPREGULATION; WESTERN BLOTTING; ANIMAL; BIOSYNTHESIS; BLOOD; BRAIN CIRCULATION; C57BL MOUSE; CEREBRAL ARTERY DISEASE; CEREBROVASCULAR ACCIDENT; DRUG EFFECT; GENE SILENCING; GENETICS; METABOLISM; PATHOLOGY;

ANIMALS; BLOOD-BRAIN BARRIER; BRAIN ISCHEMIA; CEREBROVASCULAR CIRCULATION; DISKS LARGE HOMOLOG 4 PROTEIN; EPITHELIAL-MESENCHYMAL TRANSITION; GENE SILENCING; HUMANS; INFARCTION, MIDDLE CEREBRAL ARTERY; MAGNETIC RESONANCE IMAGING; MALE; MICE; MICE, INBRED C57BL; MICRORNAS; RNA; STROKE; TIGHT JUNCTION PROTEINS; UBIQUITIN-PROTEIN LIGASES;

EID: 85040061836     PISSN: 02706474     EISSN: 15292401     Source Type: Journal    
DOI: 10.1523/JNEUROSCI.1348-17.2017     Document Type: Article

References (74)

1. Acosta SA, Tajiri N, Hoover J, Kaneko Y, Borlongan CV (2015) Intravenous bone marrow stem cell grafts preferentially migrate to spleen and abrogate chronic inflammation in stroke. Stroke 46:2616–2627. CrossRef Medline
2. Aisagbonhi O, Rai M, Ryzhov S, Atria N, Feoktistov I, Hatzopoulos AK (2011) Experimental myocardial infarction triggers canonical Wnt signaling and endothelial-to-mesenchymal transition. Dis Model Mech 4:469–483. CrossRef Medline
3. Alberts MJ (2017) Stroke treatment with intravenous tissue-type plasmino-gen activator: more proof that time is brain. Circulation 135:140–142. CrossRef Medline
4. Amin ND, Bai G, Klug JR, Bonanomi D, Pankratz MT, Gifford WD, Hinckley CA, Sternfeld MJ, Driscoll SP, Dominguez B, Lee KF, Jin X, Pfaff SL (2015) Loss of motoneuron-specific microRNA-218 causes systemic neuromuscular failure. Science 350:1525–1529. CrossRef Medline
5. Arumugam TV, Chan SL, Jo DG, Yilmaz G, Tang SC, Cheng A, Gleichmann M, Okun E, Dixit VD, Chigurupati S, Mughal MR, Ouyang X, Miele L, Magnus T, Poosala S, Granger DN, Mattson MP (2006) Gamma secretase-mediated Notch signaling worsens brain damage and functional outcome in ischemic stroke. Nat Med 12:621–623. CrossRef Medline
6. Bai YY, Gao X, Wang YC, Peng XG, Chang D, Zheng S, Li C, Ju S (2014) Image-guided pro-angiogenic therapy in diabetic stroke mouse models using a multi-modal nanoprobe. Theranostics 4:787–797. CrossRef Medline
7. Bai Y, Zhang Y, Hua J, Yang X, Zhang X, Duan M, Zhu X, Huang W, Chao J, Zhou R, Hu G, Yao H (2016) Silencing microRNA-143 protects the integrity of the blood–brain barrier: implications for methamphetamine abuse. Sci Rep 6:35642. CrossRef Medline
8. Baltan S, Morrison RS, Murphy SP (2013) Novel protective effects of his-tone deacetylase inhibition on stroke and white matter ischemic injury. Neurotherapeutics 10:798–807. CrossRef Medline
9. Boeckel JN, Jaé N, Heumüller AW, Chen W, Boon RA, Stellos K, Zeiher AM, John D, Uchida S, Dimmeler S (2015) Identification and characterization of hypoxia-regulated endothelial circular RNA. Circ Res 117:884– 890. CrossRef Medline
10. Catanese L, Tarsia J, Fisher M (2017) Acute ischemic stroke therapy overview. Circ Res 120:541–558. CrossRef Medline
11. Chang D, Wang YC, Bai YY, Lu CQ, Xu TT, Zhu L, Ju S (2015) Role of P38 MAPK on MMP activity in photothrombotic stroke mice as measured using an ultrafast MMP activatable probe. Sci Rep 5:16951. CrossRef Medline
12. Conn SJ, Pillman KA, Toubia J, Conn VM, Salmanidis M, Phillips CA, Roslan S, Schreiber AW, Gregory PA, Goodall GJ (2015) The RNA binding protein quaking regulates formation of circRNAs. Cell 160:1125–1134. CrossRef Medline
13. Cooley BC, et al. (2014) TGF-beta signaling mediates endothelial-to-mesenchymal transition (EndMT) during vein graft remodeling. Sci Transl Med 6:227-234. CrossRef Medline
14. Costes SV, Daelemans D, Cho EH, Dobbin Z, Pavlakis G, Lockett S (2004) Automatic and quantitative measurement of protein-protein colocalization in live cells. Biophys J 86:3993–4003. CrossRef Medline
15. Deng S, Huang C (2014) E3 ubiquitin ligases in regulating stress fiber, la- mellipodium, and focal adhesion dynamics. Cell Adh Migr 8:49–54. CrossRef Medline
16. Denorme F, De Meyer SF (2016) The VWF-GPIb axis in ischaemic stroke: lessons from animal models. Thromb Haemost 116:597–604. CrossRef Medline
17. Denorme F, Langhauser F, Desender L, Vandenbulcke A, Rottensteiner H, Plaimauer B, François O, Andersson T, Deckmyn H, Scheiflinger F, Kleinschnitz C, Vanhoorelbeke K, De Meyer SF (2016) ADAMTS13-mediated thrombolysis of t-PA-resistant occlusions in ischemic stroke in mice. Blood 127:2337–2345. CrossRef Medline
18. Du WW, Yang W, Chen Y, Wu ZK, Foster FS, Yang Z, Li X, Yang BB (2017) Foxo3 circular RNA promotes cardiac senescence by modulating multiple factors associated with stress and senescence responses. Eur Heart J 38: 1402–1412. CrossRef Medline
19. Fisher M, Schaebitz W (2000) An overview of acute stroke therapy: past, present, and future. Arch Intern Med 160:3196–3206. CrossRef Medline
20. Floris G, Zhang L, Follesa P, Sun T (2017) Regulatory role of circular RNAs and neurological disorders. Mol Neurobiol 54:5156–5165. CrossRef Medline
21. French AP, Mills S, Swarup R, Bennett MJ, Pridmore TP (2008) Colocalization of fluorescent markers in confocal microscope images of plant cells. Nat Protoc 3:619–628. CrossRef Medline
22. Ghosh AK, Nagpal V, Covington JW, Michaels MA, Vaughan DE (2012) Molecularbasisof cardiacendothelial-to-mesenchymal transition(EndMT): differential expression of microRNAs during EndMT. Cell Signal 24:1031–1036. CrossRef Medline
23. Gruner H, Cortés-López M, Cooper DA, Bauer M, Miura P (2016) circRNA accumulation in the aging mouse brain. Sci Rep 6:38907. CrossRef Medline
24. Hansen TB, Jensen TI, Clausen BH, Bramsen JB, Finsen B, Damgaard CK, Kjems J (2013) Natural RNA circles function as efficient microRNA sponges. Nature 495:384–388. CrossRef Medline
25. Hong Y, Wang X, Sun S, Xue G, Li J, Hou Y (2016) Progesterone exerts neuroprotective effects against Abeta-induced neuroinflammation by attenuating ER stress in astrocytes. Int Immunopharmacol 33:83–89. CrossRef Medline
26. Hu X, De Silva TM, Chen J, Faraci FM (2017) Cerebral vascular disease and neurovascular injury in ischemic stroke. Circ Res 120:449–471. CrossRef Medline
27. Jeck WR, Sharpless NE (2014) Detecting and characterizing circular RNAs. Nat Biotechnol 32:453–461. CrossRef Medline
28. Katsura A, Suzuki HI, Ueno T, Mihira H, Yamazaki T, Yasuda T, Watabe T, Mano H, Yamada Y, Miyazono K (2016) MicroRNA-31 is a positive modulator of endothelial-mesenchymal transition and associated secretory phenotype induced by TGF-beta. Genes Cells 21:99–116. CrossRef Medline
29. Kumar L, Shamsuzzama, Haque R, Baghel T, Nazir A (2016) Circular RNAs: the emerging class of non-coding RNAs and their potential role in human neurodegenerative diseases. Mol Neurobiol 54:7224–7234. CrossRef Medline
30. Kumarswamy R, Volkmann I, Jazbutyte V, Dangwal S, Park DH, Thum T (2012) Transforminggrowthfactor-beta-inducedendothelial-to-mesen-chymal transition is partly mediated by microRNA-21. Arterioscler Thromb Vasc Biol 32:361–369. CrossRef Medline
31. Lagendijk AK, Goumans MJ, Burkhard SB, Bakkers J (2011) MicroRNA-23 restricts cardiac valve formation by inhibiting Has2 and extracellular hy-aluronic acid production. Circ Res 109:649–657. CrossRef Medline
32. Laurila EM, Kallioniemi A (2013) The diverse role of miR-31 in regulating cancer associated phenotypes. Genes Chromosomes Cancer 52:1103– 1113. CrossRef Medline
33. LeBleu VS, Taduri G, O’Connell J, Teng Y, Cooke VG, Woda C, Sugimoto H, Kalluri R (2013) Origin and function of myofibroblasts in kidney fibrosis. Nat Med 19:1047–1053. CrossRef Medline
34. Lee JY, Kim HS, Choi HY, Oh TH, Yune TY (2012) Fluoxetine inhibits matrix metalloprotease activation and prevents disruption of blood-spinal cord barrier after spinal cord injury. Brain 135:2375–2389. CrossRef Medline
35. Li J, Qu X, Yao J, Caruana G, Ricardo SD, Yamamoto Y, Yamamoto H, Bertram JF (2010) Blockade of endothelial-mesenchymal transition by a Smad3 inhibitor delays the early development of streptozotocin-induced diabetic nephropathy. Diabetes 59:2612–2624. CrossRef Medline
36. Li P, Chen S, Chen H, Mo X, Li T, Shao Y, Xiao B, Guo J (2015) Using circular RNA as a novel type of biomarker in the screening of gastric cancer. Clin Chim Acta 444:132–136. CrossRef Medline
37. Li X, Zhou Q, Sunkara M, Kutys ML, Wu Z, Rychahou P, Morris AJ, Zhu H, Evers BM, Huang C (2013) Ubiquitylation of phosphatidylinositol 4-phosphate 5-kinase type I gamma by HECTD1 regulates focal adhesion dynamics and cell migration. J Cell Sci 126:2617–2628. CrossRef Medline
38. Li Y, Chopp M, Chen J, Wang L, Gautam SC, Xu YX, Zhang Z (2000) Intra-striatal transplantation of bone marrow nonhematopoietic cells improves functional recovery after stroke in adult mice. J Cereb Blood Flow Metab 20:1311–1319. CrossRef Medline
39. Liu N, Landreh M, Cao K, Abe M, Hendriks GJ, Kennerdell JR, Zhu Y, Wang LS, Bonini NM (2012) The microRNA miR-34 modulates ageing and neurodegeneration in Drosophila. Nature 482:519–523. CrossRef Medline
40. Longa EZ, Weinstein PR, Carlson S, Cummins R (1989) Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke 20:84–91. CrossRef Medline
41. Maddaluno L, Rudini N, Cuttano R, Bravi L, Giampietro C, Corada M, Fer-rarini L, Orsenigo F, Papa E, Boulday G, Tournier-Lasserve E, Chapon F, Richichi C, Retta SF, Lampugnani MG, Dejana E (2013) EndMT contributes to the onset and progression of cerebral cavernous malformations. Nature 498:492–496. CrossRef Medline
42. Malhotra K, Rayi A, Khunger M, Thompson S, Liebeskind DS (2017) Reporting compliance of stroke trials: cross-sectional analysis. J Stroke Cere-brovasc Dis 26:1472–1480. CrossRef Medline
43. Müller AH, Povlsen GK, Bang-Berthelsen CH, Kruse LS, Nielsen J, Warfvinge K, Edvinsson L (2015) Regulation of microRNAs miR-30a and miR-143 in cerebral vasculature after experimental subarachnoid hemorrhage in rats. BMC Genomics 16:119. CrossRef Medline
44. Petrini I, Barachini S, Carnicelli V, Galimberti S, Modeo L, Boni R, Sollini M, Erba PA (2017) ED-B fibronectin expression is a marker of epithelial-mesenchymal transition in translational oncology. Oncotarget 8:4914– 4921. CrossRef Medline
45. Piera-Velazquez S, Mendoza FA, Jimenez SA (2016) Endothelial to mesenchymal transition (EndoMT) in the pathogenesis of human fibrotic diseases. J Clin Med 5:E45. CrossRef Medline
46. Potenta S, Zeisberg E, Kalluri R (2008) The role of endothelial-to-mesenchymal transition in cancer progression. Br J Cancer 99:1375–1379. CrossRef Medline
47. Qin M, Liu G, Huo X, Tao X, Sun X, Ge Z, Yang J, Fan J, Liu L, Qin W (2016) Hsa_circ_0001649: a circular RNA and potential novel biomarker for hepatocellular carcinoma. Cancer Biomark 16:161–169. CrossRef Medline
48. Reijerkerk A, Lopez-Ramirez MA, van Het Hof B, Drexhage JA, Kamphuis WW, Kooij G, Vos JB, van der Pouw Kraan TC, van Zonneveld AJ, Hor-revoets AJ, Prat A, Romero IA, de Vries HE (2013) MicroRNAs regulate human brain endothelial cell-barrier function in inflammation: implications for multiple sclerosis. J Neurosci 33:6857–6863. CrossRef Medline
49. Sarkar AA, Zohn IE (2012) Hectd1 regulates intracellular localization and secretion of Hsp90 to control cellular behavior of the cranial mesen-chyme. J Cell Biol 196:789–800. CrossRef Medline
50. Shen X, Jia Z, D’Alonzo D, Wang X, Bruder E, Emch FH, De Geyter C, Zhang H (2017) HECTD1 controls the protein level of IQGAP1 to regulate the dynamics of adhesive structures. Cell Commun Signal 15:2. CrossRef Medline
51. Shi Y, Zhang L, Pu H, Mao L, Hu X, Jiang X, Xu N, Stetler RA, Zhang F, Liu X, Leak RK, Keep RF, Ji X, Chen J (2016) Rapid endothelial cytoskeletal reorganization enables early blood–brain barrier disruption and long-term ischaemic reperfusion brain injury. Nat Commun 7:10523. CrossRef Medline
52. Shi Y, Jiang X, Zhang L, Pu H, Hu X, Zhang W, Cai W, Gao Y, Leak RK, Keep RF, Bennett MV, Chen J (2017) Endothelium-targeted overexpression of heat shock protein 27 ameliorates blood–brain barrier disruption after ischemic brain injury. Proc Natl Acad Sci U S A 114:E1243–E1252. CrossRef Medline
53. Snow SJ (2016) Stroke and t-PA-triggering new paradigms of care. N Engl J Med 374:809–811. CrossRef Medline
54. Tiedt S, Prestel M, Malik R, Schieferdecker N, Duering M, Kautzky V, Stoy-cheva I, Böck J, Northoff BH, Klein M, Dorn F, Krohn K, Teupser D, Liesz A, Plesnila N, Holdt LM, Dichgans M (2017) Seq identifies circulating miR-125a-5p, miR-125b-5p and miR-143-3p as potential biomarkers for acute ischemic stroke. Circ Res 121:970–980. CrossRef Medline
55. Tominaga N, Kosaka N, Ono M, Katsuda T, Yoshioka Y, Tamura K, Lötvall J, Nakagama H, Ochiya T (2015) Brain metastatic cancer cells release microRNA-181c-containing extracellular vesicles capable of destructing blood–brain barrier. Nat Commun 6:6716. CrossRef Medline
56. Tran H, Bustos D, Yeh R, Rubinfeld B, Lam C, Shriver S, Zilberleyb I, Lee MW, Phu L, Sarkar AA, Zohn IE, Wertz IE, Kirkpatrick DS, Polakis P (2013) HectD1 E3 ligase modifies adenomatous polyposis coli (APC) with polyubiquitin to promote the APC-axin interaction. J Biol Chem 288:3753–3767. CrossRef Medline
57. Troletti CD, de Goede P, Kamermans A, de Vries HE (2016) Molecular alterations of the blood–brain barrier under inflammatory conditions: the role of endothelial to mesenchymal transition. Biochim Biophys Acta 1862:452–460. CrossRef Medline
58. Vemuganti R (2013) All’s well that transcribes well: non-coding RNAs and post-stroke brain damage. Neurochem Int 63:438–449. CrossRef Medline
59. Wang K, Long B, Liu F, Wang JX, Liu CY, Zhao B, Zhou LY, Sun T, Wang M, Yu T, Gong Y, Liu J, Dong YH, Li N, Li PF (2016) A circular RNA protects the heart from pathological hypertrophy and heart failure by targeting miR-223. Eur Heart J 37:2602–2611. CrossRef Medline
60. Wei YS, Xiang Y, Liao PH, Wang JL, Peng YF (2016) An rs4705342 TC polymorphism in the promoter of miR-143/145 is associated with a decreased risk of ischemic stroke. Sci Rep 6:34620. CrossRef Medline
61. Wermuth PJ, Carney KR, Mendoza FA, Piera-Velazquez S, Jimenez SA (2017) Endothelial cell-specific activation of transforming growth factor-beta signaling in mice induces cutaneous, visceral, and microvascular fibrosis. Lab Invest 97:806–818. CrossRef Medline
62. Wu HJ, Zhang CY, Zhang S, Chang M, Wang HY (2016) Microarray expression profile of circular RNAs in heart tissue of mice with myocardial infarction-induced heart failure. Cell Physiol Biochem 39:205–216. CrossRef Medline
63. Wu R, He Q, Chen H, Xu M, Zhao N, Xiao Y, Tu QQ, Zhang W, Bi X (2017) MicroRNA-448 promotes multiple sclerosis development through induction of Th17 response through targeting protein tyrosine phosphatase non-receptor type 2 (PTPN2). Biochem Biophys Res Commun 486:759– 766. CrossRef Medline
64. Yao H, Duan M, Buch S (2011) Cocaine-mediated induction of platelet-derived growth factor: implication for increased vascular permeability. Blood 117:2538–2547. CrossRef Medline
65. Yao H, Ma R, Yang L, Hu G, Chen X, Duan M, Kook Y, Niu F, Liao K, Fu M, Kolattukudy P, Buch S (2014) MiR-9 promotes microglial activation by targeting MCPIP1. Nat Commun 5:4386. CrossRef Medline
66. You X, Vlatkovic I, Babic A, Will T, Epstein I, Tushev G, Akbalik G, Wang M, Glock C, Quedenau C, Wang X, Hou J, Liu H, Sun W, Sambandan S, Chen T, Schuman EM, Chen W (2015) Neural circular RNAs are derived from synaptic genes and regulated by development and plasticity. Nat Neurosci 18:603–610. CrossRef Medline
67. Zeng X, Liu N, Zhang J, Wang L, Zhang Z, Zhu J, Li Q, Wang Y (2017) Inhibition of miR-143 during ischemia cerebral injury protects neurones through recovery of the hexokinase 2-mediated glucose uptake. Biosci Rep 37:BSR20170216. CrossRef Medline
68. Zhang Y, Shen K, Bai Y, Lv X, Huang R, Zhang W, Chao J, Nguyen LK, Hua J, Gan G, Hu G, Yao H (2016) Mir143-BBC3 cascade reduces microglial survival via interplay between apoptosis and autophagy: implications for methamphetamine-mediated neurotoxicity. Autophagy 12:1538–1559. CrossRef Medline
69. Zhang Y, Zhang Y, Bai Y, Chao J, Hu G, Chen X, Yao H (2017) Involvement of PUMA in pericyte migration induced by methamphetamine. Exp Cell Res 356:28–39. CrossRef Medline
70. Zhao Y, Alexandrov PN, Jaber V, Lukiw WJ (2016a) Deficiency in the ubiquitin conjugating enzyme UBE2A in Alzheimer’s disease (AD) is linked to deficits in a natural circular miRNA-7 sponge (circRNA; ciRS-7). Genes (Basel) 7:E116. CrossRef Medline
71. Zhao Y, Qiao X, Wang L, Tan TK, Zhao H, Zhang Y, Zhang J, Rao P, Cao Q, Wang Y, Wang Y, Wang YM, Lee VW, Alexander SI, Harris DC, Zheng G (2016b) Matrix metalloproteinase 9 induces endothelial-mesenchymal transition via Notch activation in human kidney glomerular endothelial cells. BMC Cell Biol 17:21. CrossRef Medline
72. Zheng Q, Bao C, Guo W, Li S, Chen J, Chen B, Luo Y, Lyu D, Li Y, Shi G, Liang L, Gu J, He X, Huang S (2016) Circular RNA profiling reveals an abundant circHIPK3 that regulates cell growth by sponging multiple miRNAs. Nat Commun 7:11215. CrossRef Medline
73. Zhu K, Pan Q, Jia LQ, Dai Z, Ke AW, Zeng HY, Tang ZY, Fan J, Zhou J (2014) MiR-302c inhibits tumor growth of hepatocellular carcinoma by suppressing the endothelial-mesenchymal transition of endothelial cells. Sci Rep 4:5524. CrossRef Medline
74. Zinchuk V, Zinchuk O, Okada T (2007) Quantitative colocalization analysis of multicolor confocal immunofluorescence microscopy images: pushing pixels to explore biological phenomena. Acta Histochem Cytochem 40: 101–111. CrossRef Medline