본문 바로가기
KERD
논문KCI 등재

MiR-322-5p Alleviates Cell Injury and Impairment of Cognitive Function in Vascular Dementia by Targeting TSPAN5

0

조회

0

다운로드

0

인용

0

참고문헌

키워드

주제분류의학일반

초록

Purpose: As the population ages, the incidence of clinical dementia has been rising around the world. It has been reported thatmicroRNAs act as key diagnostic biomarkers and targets for various neurological conditions, including dementia. MiR-322-5phas been revealed to play an important role in multiple diseases. In this study, we aimed to investigate the role and regulatorymechanism of miR-322-5p in vascular dementia. Materials and Methods: In this study, neonatal rat neurons (NRNs) were subjected to oxygen-glucose deprivation/reoxygenation(OGD/R) to induce cell injury. The animals were subjected to permanent bilateral occlusion of the carotid arteries (2-vessel occlusion,2VO) to induce the model of chronic brain hypoperfusion. Results: MiR-322-5p expression was significantly downregulated in the neurons exposed to OGD/R and the hippocampi of 2VOrats. Overexpression of miR-322-5p ameliorated cell apoptosis and the inflammatory response in vitro. In a mechanistic study, miR-322-5p was confirmed to directly target and negatively regulate tetraspanin 5 (TSPAN5) in cultured NRNs. Moreover, overexpressionof TSPAN5 could counteract the effects of miR-322-5p overexpression on cell apoptosis and the inflammatory response in OGD/Rtreatedneurons. More importantly, miR-322-5p improved cognitive ability and inhibited inflammatory production in 2VO rats. Conclusion: Overall, the results suggest that miR-322-5p alleviates vascular dementia development by targeting TSPAN5. Thisdiscovery may provide a potential therapeutic target for dementia.

Abstract

Purpose: As the population ages, the incidence of clinical dementia has been rising around the world. It has been reported thatmicroRNAs act as key diagnostic biomarkers and targets for various neurological conditions, including dementia. MiR-322-5phas been revealed to play an important role in multiple diseases. In this study, we aimed to investigate the role and regulatorymechanism of miR-322-5p in vascular dementia. Materials and Methods: In this study, neonatal rat neurons (NRNs) were subjected to oxygen-glucose deprivation/reoxygenation(OGD/R) to induce cell injury. The animals were subjected to permanent bilateral occlusion of the carotid arteries (2-vessel occlusion,2VO) to induce the model of chronic brain hypoperfusion. Results: MiR-322-5p expression was significantly downregulated in the neurons exposed to OGD/R and the hippocampi of 2VOrats. Overexpression of miR-322-5p ameliorated cell apoptosis and the inflammatory response in vitro. In a mechanistic study, miR-322-5p was confirmed to directly target and negatively regulate tetraspanin 5 (TSPAN5) in cultured NRNs. Moreover, overexpressionof TSPAN5 could counteract the effects of miR-322-5p overexpression on cell apoptosis and the inflammatory response in OGD/Rtreatedneurons. More importantly, miR-322-5p improved cognitive ability and inhibited inflammatory production in 2VO rats. Conclusion: Overall, the results suggest that miR-322-5p alleviates vascular dementia development by targeting TSPAN5. Thisdiscovery may provide a potential therapeutic target for dementia.

참고문헌 (43)

  1. Ueno M, "Blood-brain barrier damage in vascular dementia", Neuropathology, 36, pp.115~124 (2016)
  2. Di Marco LY, "Vascular dysfunction in the pathogenesis of Alzheimer’s disease--A review of endothelium-mediated mechanisms and ensuing vicious circles", Neurobiol Dis, 82, pp.593~606 (2015)
  3. Jing Z, "Chronic cerebral hypoperfusion induces vascular plasticity and hemodynamics but also neuronal degeneration and cognitive impairment", J Cereb Blood Flow Metab, 35, pp.1249~1259 (2015)
  4. Schulte C, "microRNAs in cardiovascular disease-clinical application", Clin Chem Lab Med, 55, pp.687~704 (2017)
  5. Lu TX, "MicroRNA", J Allergy Clin Immunol, 141, pp.1202~1207 (2018)
  6. Zhang J, "miR-let-7a suppresses α-synuclein-induced microglia inflammation through targeting STAT3 in Parkinson’s disease", Biochem Biophys Res Commun, 519, pp.740~746 (2019)
  7. Li J, "Targeting miR-27a", VE-cadherin interactions rescues cerebral cavernous malformations in mice, 2020, pp.18, e3000734~
  8. Gámez-Valero A, "Non-coding RNAs as sensors of oxidative stress in neurodegenerative diseases", Antioxidants(Basel), 9, pp.1095~ (2020)
  9. Aloizou AM, "Parkinson’s disease and pesticides : are microRNAs the missing link?", Sci Total Environ, 744, pp.140591~ (2020)
  10. Li J, "miR-219-5p inhibits tau phosphorylation by targeting TTBK1 and GSK-3β in Alzheimer’s disease", J Cell Biochem, 120, pp.9936~9946 (2019)
  11. Ji Y, "MiR-361-3p inhibits β-amyloid accumulation and attenuates cognitive deficits through targeting BACE1in Alzheimer’s disease", J Integr Neurosci, 18, pp.285~291 (2019)
  12. Ai J, "MicroRNA-195 protects against dementia induced by chronic brain hypoperfusion via its anti-amyloidogenic effect in rats", J Neurosci, 33, pp.3989~4001 (2013)
  13. Xie H, "MiR-9 regulates the expression of BACE1 in dementia induced by chronic brain hypoperfusion in rats", Cell Physiol Biochem, 42, pp.1213~1226 (2017)
  14. Connolly M, "miR-322-5p targets IGF-1 and is suppressed in the heart of rats with pulmonary hypertension", FEBS Open Bio, 8, pp.339~348 (2018)
  15. Bluhm B, "miR-322 stabilizes MEK1 expression to inhibit RAF", MEK, Development, pp.2017, 144[DOI]
  16. Zhang J, "MicroRNA-322 cluster promotes tau phosphorylation via targeting brain-derived neurotrophic factor", Neurochem Res, 43, pp.736~744 (2018)
  17. Sun LH, "MicroRNA-9 induces defective trafficking of Nav1. 1 and Nav1. 2 by targeting Navβ2 protein coding region in rat with chronic brain hypoperfusion", Mol Neurodegener, 10, pp.36~ (2015)
  18. Zhao T, "Ligustrazine suppresses neuron apoptosis via the Bax", Bcl-2 and caspase-3 pathway in PC12 cells and in rats with vascular dementia, 2018, pp.70, 60~70
  19. Bränström R, "Melanoma risk factors, perceived threat and intentional tanning : an international online survey", Eur J Cancer Prev, 19, pp.216~226 (2010)
  20. Roshan R, "microRNA dysregulation in polyglutamine toxicity of TATA-box binding protein is mediated through STAT1 in mouse neuronal cells", J Neuroinflammation, 14, pp.155~ (2017)
  21. Long Y, "SP1-induced SNHG14 aggravates hypertrophic response in in vitro model of cardiac hypertrophy via up-regulation of PCDH17", J Cell Mol Med, 24, pp.7115~7126 (2020)
  22. Pang B, "Myeloid-derived suppressor cells shift Th17", Treg ratio and promote systemic lupus erythematosus progression through arginase-1, TGF-βpathway, pp.Clin Sci(Lond), 2020[DOI]
  23. Qian X, "Therapeutic effect of idebenone on rats with vascular dementia via the MicroRNA-216a", RSK2, Neuropsychiatr Dis Treat, pp.2021, 17[DOI]
  24. Zhang J, "Regulatory microRNAs and vascular cognitive impairment and dementia", CNS Neurosci Ther, 26, pp.1207~1218 (2020)
  25. Liu YS, "miR-322 treatment rescues cell apoptosis and neural tube defect formation through silencing NADPH oxidase 4", CNS Neurosci Ther, 26, pp.902~912 (2020)
  26. Li W, "Dl-3-n-butylphthalide reduces cognitive impairment induced by chronic cerebral hypoperfusion through GDNF", GFRα1, Front Cell Neurosci, pp.2019, 13[DOI]
  27. Wang D, "Apelin receptor homodimer inhibits apoptosis in vascular dementia", Exp Cell Res, 407, pp.112739~ (2021)
  28. Zhang Q, "Vitexin regulates Epac and NLRP3 and ameliorates chronic cerebral hypoperfusion injury", Can J Physiol Pharmacol, 99, pp.1079~1087 (2021)
  29. Song MK, "Neurovascular integrative effects of long-term environmental enrichment on chronic cerebral hypoperfusion rat model", Brain Res Bull, 163, pp.160~169 (2020)
  30. Ghanbarabadi M, "Neuroprotective and memory enhancing effects of auraptene in a rat model of vascular dementia : experimental study and histopathological evaluation", Neurosci Lett, 623, pp.13~21 (2016)
  31. Saxena AK, "Investigation of redox status in chronic cerebral hypoperfusion-induced neurodegeneration in rats", Appl Transl Genom, 5, pp.30~32 (2015)
  32. Achkar NP, "miRNA biogenesis : a dynamic pathway", Trends Plant Sci, 21, pp.1034~1044 (2016)
  33. Mellis D, "MicroRNA-based therapeutics in cardiovascular disease : screening and delivery to the target", Biochem Soc Trans, 46, pp.11~21 (2018)
  34. Di Meco A, "MicroRNAs as therapeutic targets for Alzheimer’s disease", J Alzheimers Dis, 53, pp.367~372 (2016)
  35. Ho MF, "TSPAN5influences serotonin and kynurenine : pharmacogenomic mechanisms related to alcohol use disorder and acamprosate treatment response", Mol Psychiatry, 26, pp.3122~3133 (2021)
  36. Moretto E, "TSPAN5 enriched microdomains provide a platform for dendritic spine maturation through neuroligin-1 clustering", Cell Rep, 29, pp.1130~1146.e8 (2019)
  37. Kashef J, "Expression of the tetraspanin family members Tspan3, Tspan4, Tspan5 and Tspan7during Xenopus laevis embryonic development", Gene Expr Patterns, 13, pp.1~11 (2013)
  38. Eschenbrenner E, "TspanC8 tetraspanins differentially regulate ADAM10 endocytosis and half-life", Life Sci Alliance, 3, pp.e201900444~ (2020)
  39. Matthews AL, "Regulation of A disintegrin and metalloproteinase(ADAM)family sheddases ADAM10and ADAM17 : the emerging role of tetraspanins and rhomboids", Platelets, 28, pp.333~341 (2017)
  40. Saint-Pol J, "New insights into the tetraspanin Tspan5 using novel monoclonal antibodies", J Biol Chem, 292, pp.9551~9566 (2017)
  41. Zhou J, "Downregulation of Notch modulators, tetraspanin 5 and 10, inhibits osteoclastogenesis in vitro", Calcif Tissue Int, 95, pp.209~217 (2014)
  42. Seipold L, "Tetraspanin 3 : a central endocytic membrane component regulating the expression of ADAM10, presenilin and the amyloid precursor protein", Biochim Biophys Acta Mol Cell Res, 1864, pp.217~230 (2017)
  43. Dunn CD, "A conserved tetraspanin subfamily promotes Notch signaling in Caenorhabditis elegans and in human cells", Proc Natl Acad Sci U S A, 107, pp.5907~5912 (2010)

관련 논문AI추천

Emerging Roles of microRNAs in Ischemic Stroke: As Possible Therapeutic AgentsHadi Fathi Moghaddam, Maryam Farzaneh, Seyed Esmaeil Khoshnam, William Winlow, Yaghoob Farbood대한뇌졸중학회 · 대한뇌졸중영문학회지2017 · 제19권 제2호MiR-494-3p Upregulation Exacerbates Cerebral Ischemia Injury by Targeting Bhlhe40Dandan Ji, Feng Zhi, Jie Bao, Lingjiang Sun, Qin Zhu, Tong Ni, Yu Fang, Zigang Zhu연세대학교의과대학 · Yonsei Medical Journal2022 · 제63권 제4호Inhibition of miR-128 Abates Aβ-Mediated Cytotoxicity by Targeting PPAR-γ via NF-κB Inactivation in Primary Mouse Cortical Neurons and Neuro2a CellsLijiao Geng, Tao Zhang, Wei Liu, Yong Chen연세대학교의과대학 · Yonsei Medical Journal2018 · 제59권 제9호BDNF Signaling in Vascular Dementia and Its Effects on Cerebrovascular Dysfunction, Synaptic Plasticity, and Cholinergic System Abnormality송주현한국지질동맥경화학회 · 지질·동맥경화학회지2024 · 제13권 제2호Partial Preventive Effect of Ibuprofen in a Mouse Model of Vascular Cognitive Impairment Induced by Unilateral Common Carotid Artery Occlusion이진수, Byoung Joo Gwag, Doo Soon Im, Gyeong Joon Moon, In Soo Joo, Ji Man Hong, So Young Moon대한치매학회 · Dementia and Neurocognitive Disorders(대한치매학회지)2009 · 제8권 제2호Diagnostic and Prognostic Circulating MicroRNA in Acute Stroke: A Systematic and Bioinformatic Analysis of Current EvidenceDavid J. Williams, Elisabeth Jirström, Jorin Bejleri, Paul Donovan, Shona Pfeiffer대한뇌졸중학회 · 대한뇌졸중영문학회지2021 · 제23권 제2호

이 간행물의 다른 논문 (11건)