LncRNA ANRIL Silencing Alleviates High Glucose-Induced Inflammation, Oxidative Stress, and Apoptosis via Upregulation of MME in Podocytes

Inflammation, Journal Year: 2020, Volume and Issue: 43(6), P. 2147 - 2155

Published: July 3, 2020

Language: Английский

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Downregulation of miR-218 by porcine reproductive and respiratory syndrome virus facilitates viral replication via inhibition of type I interferon responses

Journal of Biological Chemistry, Journal Year: 2021, Volume and Issue: 296, P. 100683 - 100683

Published: Jan. 1, 2021

Porcine reproductive and respiratory syndrome virus (PRRSV) is a devastating pathogen in the swine industry worldwide. miRNAs are reported to be involved virus–host interaction. Here, we used high-throughput sequencing miRNA inhibitors screen possible that can inhibit PRRSV infection on its target cell, porcine alveolar macrophages. We observed miR-218 was downregulated upon infection, knockdown of significantly enhanced replication. Overexpression resulted decrease replication, this overexpression did not alter viral genomic RNA levels, but rather increased antiviral interferon signaling. Further analysis revealed regulated replication by directly targeting suppressor cytokine signaling 3 (SOCS3), JAK2 kinase inhibitor. Knockdown endogenous SOCS3 expression led augmentation type I genes decreased vice versa. During vivo vitro, cellular upregulated, further supporting inverse correlation between expression. The data depletion combination with inhibition suggested activity required SOCS3-mediated pathway. Similarly, negatively Marc-145 cells, as well epidemic diarrhea transmissible gastroenteritis Vero ST cells respectively. Taken together, these results demonstrate PRRSV-induced downregulation serves response may provide novel therapeutic for treatment other infections. an enveloped, single-stranded positive virus, belonging family Arteriviridae order Nidovirales (1Cavanagh D. Nidovirales: A new comprising Coronaviridae arteriviridae.Arch. Virol. 1997; 142: 629-633PubMed Google Scholar, 2Meulenberg J.J. PRRSV, virus.Vet. Res. 2000; 31: 11-21PubMed Scholar). etiological agent (PRRS), which characterized failure sows severe symptoms piglets growing pigs. PRRS first described United States 1987 Europe 1990 (3Collins J.E. Benfield D.A. Christianson W.T. Harris L. Hennings J.C. Shaw D.P. Goyal S.M. McCullough S. Morrison R.B. Joo H.S. Gorcyca D.C. Isolation infertility (isolate ATCC VR-2332) North America experimental reproduction disease gnotobiotic pigs.J. Vet. Diagn. Invest. 1992; 4: 117-126Crossref PubMed Scopus (601) 4Meulenberg Hulst M.M. de Meijer E.J. Moonen P.L. den Besten A. Kluyver E.P. Wensvoort G. Moormann R.J. Lelystad causative abortion (PEARS), related LDV EAV.Virology. 1993; 192: 62-72Crossref (623) Scholar), since then has spread around most pig-producing countries become economically To control disease, researchers have developed different vaccines. However, due high antigenic heterogeneity use current vaccines some limitations (5Rappe García-Nicolás O. Flückiger F. Thür B. Hofmann M.A. Summerfield Ruggli N. Heterogeneous properties nucleocapsid.Vet. 2016; 47: 117Crossref (10) 6Vu H.L.X. Pattnaik A.K. Osorio F.A. Strategies broaden cross-protective efficacy against Microbiol. 2017; 206: 29-34Crossref (25) Therefore, it worthwhile explore immune regulatory molecules from host's perspective. miRNAs, class noncoding RNAs ∼22 nucleotides, play important roles regulation gene at posttranscriptional level. initially transcribed genome primary processed into final mature through series intermediates biogenesis machinery. Mature incorporated RNA-induced silencing complex where bind their mRNAs result mRNA destabilization and/or translational repression (7Dong H. Lei J. Ding Wen Y. Ju Zhang X. MicroRNA: Function, detection, bioanalysis.Chem. Rev. 2013; 113: 6207-6233Crossref (686) 8Mohr A.M. Mott J.L. Overview microRNA biology.Semin. Liver Dis. 2015; 35: 3-11Crossref (467) In animals, 5'-proximal seed region (at nucleotides 2–8) binds complementary sequences within 3'-untranslated (3'UTR) (9Eulalio Huntzinger E. Izaurralde Getting root miRNA-mediated silencing.Cell. 2008; 132: 9-14Abstract Full Text PDF (730) It estimated more than half protein coding mammals (10Chekulaeva M. Filipowicz W. Mechanisms post-transcriptional animal cells.Curr. Opin. Cell Biol. 2009; 21: 452-460Crossref (524) thus participate processes including DNA reparation, cell proliferation differentiation, ontogenesis (11Krol Loedige I. widespread biogenesis, function decay.Nat. Genet. 2010; 11: 597-610Crossref (3059) 12Bartel MicroRNAs: Target recognition functions.Cell. 136: 215-233Abstract (14172) 13Vidigal J.A. Ventura biological functions miRNAs: Lessons studies.Trends 25: 137-147Abstract (272) addition, also repertoire interactions affect (14Barbu M.G. Condrat C.E. Thompson Bugnar O.L. Cretoiu Toader O.D. Suciu Voinea S.C. MicroRNA Involvement pathways during infection.Front Dev 2020; 8: 143Crossref (23) 15Duan Wang Sun Yan Yang Understanding cross-talk host poultry perspectives microRNA.Poult. Sci. 99: 1838-1846Crossref (4) 16Trobaugh D.W. Klimstra W.B. pathogenesis.Trends Mol. Med. 23: 80-93Abstract (139) Ⅰ interferons (IFNs) activity, such IFN-α IFN-β, produced fibroblasts monocytes (17Muller U. Steinhoff Reis L.F. Hemmi Pavlovic Zinkernagel R.M. Aguet Functional role II defense.Science. 1994; 264: 1918-1921Crossref (1895) Once released, IFNs cognate receptors activate Jak-STAT pathway induce transcription IFN-stimulated (ISGs) (18Schoggins J.W. Rice C.M. Interferon-stimulated effector functions.Curr. 2011; 1: 519-525Crossref (685) 19Sadler A.J. Williams B.R. Interferon-inducible effectors.Nat. Immunol. 559-568Crossref (1398) 20Schneider W.M. Chevillotte M.D. genes: web defenses.Annu. 2014; 32: 513-545Crossref (1291) Recent evidence reveals regulate several viruses managing production ISGs (21Forster Tate Hertzog P.J. interferon-regulated transcripts modulators innate response.Front 6: 334Crossref (81) 22Wong R.R. Abd-Aziz Affendi Poh C.L. Role microRNAs responses dengue infection.J. Biomed. 27: 4Crossref (19) Likewise, few miRNA-23, miR-26a, miR-30c, miRNA-373, attribute modulate IFN or (23Zhang Q. Huang C. Gao Liu H.C. Tang Feng W.H. MicroRNA-30c modulates facilitate JAK1.J. 196: 2272-2282Crossref (52) 24Li Wei Z. Zhou Jiang Yu Zheng Tong Shan T. Xia Host miR-26a suppresses upregulating interferons.Virus 195: 86-94Crossref (42) 25Chen Shi Deng R. G.P. 373 facilitates negative induction.J. 91e01311-16Crossref (28) Since details just begun emerge, comprehensive investigation pathogenesis will contribute better understanding host–pathogen interactions. present study, obtained differently expressed profiles deep HP-PRRSV-infected Based screening data, investigated induction vitro vivo. found regulates SOCS3, clarifying one molecular mechanisms underlying pathogenesis. investigate utilized profile macrophages (PAMs) 24 h postinfection (hpi) HP-PRRSV strain HuN4. Mock-treated PAMs were control. top 100 mock-treated shown Figure 1A. Comparing previously them figure, miR-23, miR-378, miR-22, let-7f, miR-29a, miR-181, miR-505, miR-125b (26Du Nan Xiao Zhao E.M. Antiviral strategies infection.Trends 968-979Abstract (35) suggesting our reliable. After treatment, downregulated, volcano plot (Fig. 1B). Among them, seven miR-339-5p, miR-99b, miR-365-5p, miR-345, miR-27b-3p, all ranked inside 1C). Like findings, Zhen et al. miR-378 (27Zhen Liang Xu Su Identification differentially non-coding Tongcheng large white pigs Responded PRRSV.Sci. Rep. 2018; 15621Crossref (6) confirmed western blot 1D). Next, effect explored blocking using specific inhibitors. transfected each h, inoculated MOI 0.1 h. Relative quantitative PCR (qPCR) showed had levels 1E), indicating four Consistent been effective inhibitor increase RNA, titers collected supernatants measured TCID50 assay, marked contrast 2A). Meanwhile, commercial mimic overexpress PAMs. At post transfection, infected additional qPCR reduced load compared 2B). assay displayed significant 2C). No toxicity concentrations <150 nM evident S1). These findings indicate potential determine whether low-virulent similar expression, treated attenuated live vaccine HuN4-F112, Marc-145-adaptive cannot efficiently replicate (28Tian Z.J. An T.Q. Y.J. Peng J.M. Hu S.P. T.C. Y.F. G.Z. based highly pathogenic (HP-PRRSV) protects HP-PRRS.Vet. 138: 34-40Crossref (96) level HuN4-F112-treated group 2D). UV-inactivated HuN4 2E), miR-218. Furthermore, identified dynamic changes stages infection. As 2F, attachment expression; 2G, occurred after entered biosynthesis (after two hpi). Altogether, replication-mediated Previous studies demonstrated happen (29Bernier Sagan Diverse Host⁻Virus Interface.Viruses. 10: 440-465Crossref (38) 30Skalsky R.L. Cullen Viruses, microRNAs, interactions.Annu. 64: 123-141Crossref (470) cycle positive-sense intermediate, negative-sense molecule, templates synthesis (31Fang Snijder replicase: Exploring multifunctionality intriguing set nonstructural proteins.Virus 154: 61-76Crossref (248) Thus, uncover sequence there least paired regions negative/positive-sense 3A). test targets acts direct factor, 2 8 followed detecting RNAs. 3, B C, RNA. Given PAMs, mechanisms. Type key quantities trigger (32Mesev E.V. LeDesma R.A. Ploss Decoding III signalling infection.Nat. 2019; 914-924Crossref (95) next determined could modify IFN. transcriptional IFN-β ISGs. ISG15, 2′-5′-oligoadenylate synthetase-like (OASL), GBP1, IFIT1, IFITM3 presence 3D). suggest modulating response. mechanism response, TargetScan miRDB One putative binding site 3'UTR critical regulator inflammation (33Carow Rottenberg M.E. Major inflammation.Front 5: 58Crossref (218) pairing 4A. validate association miR-218, containing predicted cloned dual-luciferase reporter vector pmirGLO, same mutations constructed obtain mutant plasmid (Supplementary material HEK-293 T cotransfected empty vector, wild-type 48 inhibited luciferase plasmid-transfected relative contrast, transfection abolished 4B), interact 3'UTR. verify determined. following 4C). Western markedly 4D). incubating mock time points, assessed qPCR. 4E, hpi. Whereas 6 hpi reached peak correlated vitro. confirm samples examined. Total extracted lung mock, 21 days lower HuN4-inoculated controls HuN4-F112 On contrary, comparison 4F). virus-induced leads might impair Moreover, genetic modification methods. SOCS3-specific siRNA siRNA. detergent lysates clear reduction 5A). greatly 5B). titer 5C). another introduced repeat above experiments. S2). tried detectable (data shown), low efficiency. immortalized PRRSV. overexpressed successfully 5D). 5E, 5F). modifying OASL, GBP1 analyzed three ISGs, (Figs. 5G S3). pathway, eukaryotic stimulation. 5H). Overall, induced-miR-218 upregulates serve promote elucidate carried out interference effectively promoted titer. remarkably suppressed 6, B). When SOCS3-depleted both blocked beneficial impairs examined cells. monolayers fixed IFA analysis, notably PRRSV-positive 7A). inhibitor-treated 7B). Transfection consequently augmented 7C). when mimic, number mimic-treated control-treated 7D). 7E), cultures measuring 7F). suppression consistent evolutionarily conserved lines. evaluated members Nidovirales, PEDV (porcine virus) TGEV (transmissible virus). E6 Cells supernatant harvested indicated 7G). above, 7H, loads TCID50. broad-spectrum property. line defense system, glycoproteins strong immunomodulatory activities. published susceptible (34Brockmeier S.L. Loving Eberle K.C. Hau S.J. Buckley Van Geelen Montiel N.A. Nicholson Lager K.M. Interferon alpha inhibits live-attenuated preventing development adaptive swine.Vet. 212: 48-51Crossref (9) 35Luo Fang Jin Chen (PRRSV).An

Language: Английский

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miR - 218 - 2 regulates cognitive functions in the hippocampus through complement component 3–dependent modulation of synaptic vesicle release

Proceedings of the National Academy of Sciences, Journal Year: 2021, Volume and Issue: 118(14)

Published: March 29, 2021

microRNA-218 (miR-218) has been linked to several cognition related neurodegenerative and neuropsychiatric disorders. However, whether miR-218 plays a direct role in cognitive functions remains unknown. Here, using the knockout (KO) mouse model sponge/overexpression approaches, we showed that miR-218-2 but not miR-218-1 could bidirectionally regulate contextual spatial memory mice. Furthermore, deficiency induced deficits morphology presynaptic neurotransmitter release hippocampus impair long term potentiation. Combining RNA sequencing analysis luciferase reporter assay, identified complement component 3 (C3) as main target gene of functions. Finally, restoring C3 activity KO mice rescue synaptic learning deficits. Therefore, played an important through C3, which can be mechanism for defective neuronal

Language: Английский

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Circular RNAs; powerful microRNA sponges to overcome diabetic nephropathy

Pathology - Research and Practice, Journal Year: 2021, Volume and Issue: 227, P. 153618 - 153618

Published: Sept. 15, 2021

Language: Английский

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Understanding the lncRNA/miRNA-NFκB regulatory network in diabetes mellitus: From function to clinical translation

Diabetes Research and Clinical Practice, Journal Year: 2023, Volume and Issue: 202, P. 110804 - 110804

Published: June 25, 2023

Language: Английский

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Research Progress of Traditional Chinese Medicine in the Treatment of Diabetic Nephropath

Advances in Clinical Medicine, Journal Year: 2025, Volume and Issue: 15(04), P. 3060 - 3069

Published: Jan. 1, 2025

Language: Английский

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MiR-214-3p targets RIPK1 to regulate pyroptosis and vascular endothelial function in diabetic ketoacidosis: mechanistic insights

Gene, Journal Year: 2025, Volume and Issue: unknown, P. 149555 - 149555

Published: May 1, 2025

Language: Английский

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Diagnostic Value and Mechanism of Action of Serum miR‐1281 Involved in T2DM and Complications of DKD

Nephrology, Journal Year: 2025, Volume and Issue: 30(5)

Published: May 1, 2025

ABSTRACT Objective To research the diagnostic value and mechanism of miR‐1281 involved in type 2 diabetes mellitus (T2DM) diabetic kidney disease (DKD). Methods One hundred eighteen patients with T2DM (68 DKD patients) 35 healthy individuals were included. Fasting venous blood one‐time morning urine collected for biochemical testing. RT‐qPCR detected expression, ROC curve assessed DKD, logistic regression predicted risk factors affecting progression DKD. ELISA analysed inflammatory cytokine Pearson correlation its relevance to miR‐1281. CCK8 cell proliferation flow cytometry recorded apoptosis. Results was upregulated increased more significantly patients. The curves indicated that had predicting closely related pathological characteristics results showed expression a factor progression. cytokines (IL‐6, IL‐18, TNF‐α) T2DM, analysis positive between expression. high‐glucose environment promoted proliferation, decreased apoptosis, levels, but transfection inhibitor resisted adverse effects on cells. Conclusion promotes glomerular inhibits increases level intracellular inflammation, leading impaired renal function

Language: Английский

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The novel circ_0028171/miR-218-5p/IKBKB axis promotes osteosarcoma cancer progression

Cancer Cell International, Journal Year: 2020, Volume and Issue: 20(1)

Published: Oct. 6, 2020

Abstract Background Recently, it has been demonstrated that circular RNA (circRNA) contributes to the production and progression in human cancer. However, specific function underlying mechanism of circ_0028171 osteosarcoma (OS) still remain largely unclear require be investigated. Methods In our study, we confirmed differentially expressed circRNAs by microarray analysis normal bone cells vs. OS cell lines. The expression circ-0028171 was measured qRT-PCR. Nuclear-cytoplasmic fractionation employed identify localization circ-0028171, RNase R actinomycin D treatment were used prove its characteristic. vitro experiments, such as CCK-8 method, count, colony formation, transwell migration invasion assays, vivo tumor models adopted evaluate effect circ_0028171. Further, luciferase reporter, RIP pull-down assays conducted confirm binding sites with miR-218-5p. Results We found displayed a remarkably higher both tissues Circ_0028171 mainly located cytoplasm stable cyclic transcript. Knockdown suppressed growth vivo, while up-regulated enhanced proliferation, abilities OS. Several mechanistic experiments revealed served sponge miR-218-5p increase IKBKB expression. Conclusions research reveals might promote malignant behavior through miR-218-5p/IKBKB axis, which could potential novel marker for early diagnosis

Language: Английский

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Mechanism of miR-365 in regulating BDNF-TrkB signal axis of HFD/STZ induced diabetic nephropathy fibrosis and renal function

International Urology and Nephrology, Journal Year: 2021, Volume and Issue: 53(10), P. 2177 - 2187

Published: April 21, 2021

Language: Английский

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