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  • 1 Debreceni Egyetem, Általános Orvostudományi Kar, Debrecen, Móricz Zs. krt. 22., 4032
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Absztrakt:

A mikro-RNS-ek (miRNS) 18–25 nukleotid hosszúságú, egyszálú, endogén, nem kódoló kis RNS-ek, melyek fontos szerepet játszanak a génexpresszió poszttranszkripcionális szinten történő finomhangolásában. A fehérjét kódoló gének körülbelül 90%-a áll a miRNS-ek regulációs hatása alatt, melyek így kulcsszerepet játszanak különböző biológiai folyamatokban, többek között a sejtfejlődés, -proliferáció, -differenciálódás, -apoptózis és az immunhomeosztázis szabályozása során. Egyes miRNS-ek expressziójában bekövetkező változások hozzájárulhatnak számos kórkép, köztük szisztémás autoimmun betegségek kialakulásához is. A jelen tanulmányban összefoglaljuk a miRNS-ek biogenezisét, az immunrendszer szabályozásában betöltött szerepüket, illetve áttekintjük a legújabb kutatási eredményeket szisztémás lupus erythematosusban, primer Sjögren-szindrómában, rheumatoid arthritisben és szisztémás sclerosisban. A jövőben a miRNS-ek nemcsak mint biomarkerek segíthetnek majd a diagnózis és prognózis meghatározásában, hanem potenciális terápiás célpontokként is alkalmazhatók lehetnek az autoimmun betegségek modern terápiájában. Orv Hetil. 2019; 160(15): 563–572.

  • 1

    Chen JQ, Papp G, Szodoray P, et al. The role of microRNAs in the pathogenesis of autoimmune diseases. Autoimmun Rev. 2016; 15: 1171–1180.

  • 2

    Nagy Z, Decmann Á, Perge P, et al. Pathogenic and diagnostic roles of microRNAs in adrenocortical tumours. [A mikro-RNS-ek patogenetikai és diagnosztikai szerepe mellékvesekéreg-carcinomában.] Orv Hetil. 2018; 159: 245–251. [Hungarian]

  • 3

    Decmann Á, Perge P, Nagy Z, et al. Circulating microRNAs in the diagnostics of endocrine neoplasms. [Keringő mikroRNS-ek az endokrin daganatok diagnosztikájában.] Orv. Hetil. 2017; 158: 483–490. [Hungarian]

  • 4

    Graves P, Zeng Y. Biogenesis of mammalian microRNAs: a global view. Genomics Proteomics Bioinformatics 2012; 10: 239–245.

  • 5

    Yi R, Qin Y, Macara IG, et al. Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs. Genes Dev. 2003; 17: 3011–3016.

  • 6

    Westholm JO, Lai EC. Mirtrons: microRNA biogenesis via splicing. Biochimie 2011; 93: 1897–1904.

  • 7

    Carthew RW, Sontheimer EJ. Origins and mechanisms of miRNAs and siRNAs. Cell 2009; 136: 642–655.

  • 8

    Baulina NM, Kulakova OG, Favorova OO. MicroRNAs: the role in autoimmune inflammation. Acta Naturae 2016; 8: 21–33.

  • 9

    Chen JQ, Szodoray P, Zeher M. Toll-like receptor pathways in autoimmune diseases. Clin Rev Allergy Immunol. 2016; 50: 1–17.

  • 10

    Hou J, Wang P, Lin L, et al. MicroRNA-146a feedback inhibits RIG-I-dependent type I IFN production in macrophages by targeting TRAF6, IRAK1, and IRAK2. J Immunol. 2009; 183: 2150–2158.

  • 11

    Liu G, Friggeri A, Yang Y, et al. miR-147, a microRNA that is induced upon Toll-like receptor stimulation, regulates murine macrophage inflammatory responses. Proc Natl Acad Sci USA 2009; 106: 15819–15824.

  • 12

    Tili E, Michaille JJ, Cimino A, et al. Modulation of miR-155 and miR-125b levels following lipopolysaccharide/TNF-alpha stimulation and their possible roles in regulating the response to endotoxin shock. J Immunol. 2007; 179: 5082–5089.

  • 13

    Cobb BS, Nesterova TB, Thompson E, et al. T cell lineage choice and differentiation in the absence of the RNase III enzyme Dicer. J Exp Med. 2005; 201: 1367–1373.

  • 14

    Muljo SA, Ansel KM, Kanellopoulou C, et al. Aberrant T cell differentiation in the absence of Dicer. J Exp Med. 2005; 202: 261–269.

  • 15

    Li J, Wan Y, Ji Q, et al. The role of microRNAs in B-cell development and function. Cell Mol Immunol. 2013; 10: 107–112.

  • 16

    Gonzalez-Martin A, Adams BD, Lai M, et al. The microRNA miR-148a functions as a critical regulator of B cell tolerance and autoimmunity. Nat Immunol. 2016; 17: 433–440.

  • 17

    Szántó A, Szodoray P, Kiss E, et al. Clinical, serologic, and genetic profiles of patients with associated Sjögren’s syndrome and systemic lupus erythematosus. Hum Immunol. 2006; 67: 924–930.

  • 18

    Martini D, Gallo A, Vella S, et al. Cystatin S – a candidate biomarker for severity of submandibular gland involvement in Sjögren’s syndrome. Rheumatology 2017; 56: 1031–1038.

  • 19

    Wang Y, Zhang G, Zhang L, et al. Decreased microRNA-181a and -16 expression levels in the labial salivary glands of Sjögren syndrome patients. Exp Ther Med. 2018; 15: 426–432.

  • 20

    Alevizos I, Alexander S, Turner RJ, et al. MicroRNA expression profiles as biomarkers of minor salivary gland inflammation and dysfunction in Sjögren’s syndrome. Arthritis Rheum. 2011; 63: 535–544.

  • 21

    Gourzi VC, Kapsogeorgou EK, Kyriakidis NC, et al. Study of microRNAs (miRNAs) that are predicted to target the autoantigens Ro/SSA and La/SSB in primary Sjögren’s syndrome. Clin Exp Immunol. 2015; 182: 14–22.

  • 22

    Zilahi E, Tarr T, Papp G, et al. Increased microRNA-146a/b, TRAF6 gene and decreased IRAK1 gene expressions in the peripheral mononuclear cells of patients with Sjögren’s syndrome. Immunol Lett. 2012; 141: 165–168.

  • 23

    Shi H, Zheng LY, Zhang P, et al. miR-146a and miR-155 expression in PBMCs from patients with Sjögren’s syndrome. J Oral Pathol Med. 2014; 43: 792–797.

  • 24

    Honarpisheh M, Köhler P, von Rauchhaupt E, et al. The involvement of microRNAs in modulation of innate and adaptive immunity in systemic lupus erythematosus and lupus nephritis. J Immunol Res. 2018; 2018: 4126106.

  • 25

    Lai NS, Koo M, Yu CL, et al. Immunopathogenesis of systemic lupus erythematosus and rheumatoid arthritis: the role of aberrant expression of non-coding RNAs in T cells. Clin Exp Immunol. 2016; 187: 327–336.

  • 26

    Meinzinger J, Jäck HM, Pracht K. miRNA meets plasma cells “How tiny RNAs control antibody responses”. Clin Immunol. 2018; 186: 3–8.

  • 27

    Xia Y, Tao JH, Fang X, et al. MicroRNA-326 upregulates B cell activity and autoantibody production in lupus disease of MRL/Ipr mice. Mol Ther Nucleic Acids 2018; 11: 284–291.

  • 28

    Husakova M. MicroRNAs in the key events of systemic lupus erythematosus pathogenesis. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2016; 160: 327–342.

  • 29

    Liu D, Zhang N, Zhang J, et al. miR-410 suppresses the expression of interleukin-6 as well as renal fibrosis in the pathogenesis of lupus nephritis. Clin Exp Pharmacol Physiol. 2016; 43: 616–625.

  • 30

    Qingjuan L, Xiaojuan F, Wei Z, et al. miR-148a-3p overexpression contributes to glomerular cell proliferation by targeting PTEN in lupus nephritis. Am J Physiol Cell Physiol. 2016; 310: C470–C478.

  • 31

    Wang W, Mou S, Wang L, et al. Up-regulation of serum MiR-130b-3p level is associated with renal damage in early lupus nephritis. Sci Rep. 2015; 5: 12644.

  • 32

    Solé C, Cortés-Hernández J, Felip ML, et al. miR-29c in urinary exosomes as predictor of early renal fibrosis in lupus nephritis. Nephrol Dial Transplant. 2015; 30: 1488–1496.

  • 33

    Perez-Hernandez, J, Forner MJ, Pinto C, et al. Increased urinary exosomal microRNAs in patients with systemic lupus erythematosus. PLoS ONE 2015; 10: e0138618.

  • 34

    Xiao G, Zuo X: Epigenetics in systemic lupus erythematosus. Biomed Rep. 2016; 4: 135–139.

  • 35

    Liu L, Liu Y, Yuan M, et al. Elevated expression of microRNA- 873 facilitates Th17 differentiation by targeting forkhead box O1 (Foxo1) in the pathogenesis of systemic lupus erythematosus. Biochem Biophys Res Commun. 2017; 492: 453–460.

  • 36

    Aslani S, Sobhani S, Gharibdoost F, et al. Epigenetics and pathogenesis of systemic sclerosis; the ins and outs. Human Immunol. 2018; 79: 178–187.

  • 37

    Chouri E, Servaas NH, Bekker CP. Serum microRNA screening and functional studies reveal miR-483-5p as a potential driver of fibrosis in systemic sclerosis. J Autoimmun. 2018; 89: 162–170.

  • 38

    Artlett CM, Sassi-Gaha S, Hope JL, et al. Mir-155 is overexpressed in systemic sclerosis fibroblasts and is required for NLRP3 inflammasome-mediated collagen synthesis during fibrosis. Arthritis Res Ther. 2017; 19: 144.

  • 39

    Ciechomska M, O’Reilly S, Suwara M, et al. MiR-29a reduces TIMP-1 production by dermal fibroblasts via targeting TGF-β activated kinase 1 binding protein 1, implications for systemic sclerosis. PLoS ONE 2014; 9: e115596.

  • 40

    Jafarinejad-Farsangi S, Farazmand A, Mahmoudi M, et al. MicroRNA-29a induces apoptosis via increasing the Bax : Bcl-2 ratio in dermal fibroblasts of patients with systemic sclerosis. Autoimmunity 2015; 48: 369–378.

  • 41

    Iwamoto N, Vettori S, Maurer B, et al. Downregulation of miR-193b in systemic sclerosis regulates the proliferative vasculopathy by urokinase-type plasminogen activator expression. Ann Rheum Dis. 2016; 75: 303–310.

  • 42

    Moran-Moguel MC, Petarra-del Rio S, Mayorquin-Galvan EE, et al. Rheumatoid arthritis and miRNAs: a critical review through a functional view. J Immunol Res. 2018; 2018: 2474529.

  • 43

    Pál I, Pusztai A, Csomor P, et al. Experience with a rheumatoid arthritis biobank: analysis of biological samples and clinical data of 204 patients. [Rheumatoid arthritises biobankkal szerzett tapasztalataink: 204 beteg biológiai mintáinak és klinikai adatainak összevetése.] Orv Hetil. 2017; 158: 270–277. [Hungarian]

  • 44

    Ogando J, Tardáguila M, Díaz-Alderete A, et al. Notch-regulated miR-223 targets the aryl hydrocarbon receptor pathway and increases cytokine production in macrophages from rheumatoid arthritis patients. Sci Rep. 2016; 6: 20223.

  • 45

    Hu J, Zhai C, Hu J, et al. MiR-23a inhibited IL-17-mediated proinflammatory mediators expression via targeting IKKα in articular chondrocytes. Int Immunopharmacol. 2017; 43: 1–6.

  • 46

    Tang X, Yin K, Zhu H, et al. Correlation between the expression of microRNA-301a-3p and the proportion of Th17 cells in patients with rheumatoid arthritis. Inflammation 2016; 39: 759–767.

  • 47

    Jin S, Chen H, Li Y, et al. Maresin 1 improves the Treg/Th17 imbalance in rheumatoid arthritis through miR-21. Ann Rheum Dis. 2018; 77: 1644–1652.

  • 48

    Mookherjee N, El-Gabalawy HS. High degree of correlation between whole blood and PBMC expression levels of miR-155 and miR-146a in healthy controls and rheumatoid arthritis patients. J Immunol Methods 2013; 400–401: 106–110.

  • 49

    Wang L, Song G, Zheng Y, et al. miR-573 is a negative regulator in the pathogenesis of rheumatoid arthritis. Cell Mol Immunol. 2016; 13: 839–849.

  • 50

    Liu J, Fei D, Xing J, et al. MicroRNA-29a inhibits proliferation and induces apoptosis in rheumatoid arthritis fibroblast-like synoviocytes by repressing STAT3. Biomed Pharmacother. 2017; 96: 173–181.

  • 51

    Li S, Jin Z, Lu X. MicroRNA-192 suppresses cell proliferation and induces apoptosis in human rheumatoid arthritis fibroblast-like synoviocytes by downregulating caveolin 1. Mol Cell Biochem. 2017; 432: 123–130.

  • 52

    Li H, Guan SB, Lu Y, et al. MiR-140-5p inhibits synovial fibroblasts proliferation and inflammatory cytokines secretion through targeting TLR4. Biomed Pharmacother. 2017; 96: 208–214.

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