Abstract
Diabetes mellitus, defined as long-standing hyperglycemic conditions caused by a defect in insulin production and activity, has become a major healthcare burden as the number of catastrophic and life-threatening complications rises. Microvascular complications (neuropathy, retinopathy, and nephropathy), and also diabetes-related macrovascular complications are common problems that arise as the life expectancy of diabetic patients has increased despite improved treatment options. While it is impossible to pinpoint the specific crucial timing when the complications become fully entrenched, looking for novel sensitive biomarkers to identify physiological changes in the initial stages would be needed. An increasing amount of data shows that miRNAs, particularly miRNA146a, are stable in a range of body fluids and can be used to identify pathogenic changes at the cellular or tissue level. In this brief review, we highlight the important functioning of miRNA146a and its putative target of action in diabetic microvascular and cardiovascular complications. A decrease in miRNA146a levels may play a critical role in the onset and development of diabetes complications, whereas its anti-inflammatory properties were revealed to be associated with the pathogenesis of numerous diabetic complications, including diabetic nephropathy, retinopathy, neuropathy, and diabetes-related cardiovascular disorders, even tending to be a potential biomarker of the disease's inflammatory status.
[http://dx.doi.org/10.1007/s40200-020-00641-x] [PMID: 33520871]
[http://dx.doi.org/10.1038/s41574-019-0254-y] [PMID: 31534209]
[http://dx.doi.org/10.3389/fendo.2019.00592]
[http://dx.doi.org/10.1038/s41574-020-0355-7] [PMID: 32398822]
[http://dx.doi.org/10.1038/nrendo.2017.151] [PMID: 29219149]
[http://dx.doi.org/10.2174/1573399815666181204145806] [PMID: 30514191]
[http://dx.doi.org/10.1038/s41581-020-0278-5] [PMID: 32398868]
[http://dx.doi.org/10.2337/db19-1070] [PMID: 32385057]
[http://dx.doi.org/10.3389/fendo.2018.00402]
[http://dx.doi.org/10.1007/s00125-015-3680-y] [PMID: 26155747]
[http://dx.doi.org/10.1373/clinchem.2010.147405] [PMID: 20847327]
[http://dx.doi.org/10.1111/j.1349-7006.2010.01650.x] [PMID: 20624164]
[http://dx.doi.org/10.1038/nrclinonc.2011.76] [PMID: 21647195]
[PMID: 23592910]
[http://dx.doi.org/10.3389/fimmu.2018.01377] [PMID: 29988529]
[PMID: 29682487]
[http://dx.doi.org/10.2337/db11-0478] [PMID: 21885871]
[http://dx.doi.org/10.1038/nrm1644] [PMID: 15852042]
[http://dx.doi.org/10.1038/nrg2455] [PMID: 18852696]
[PMID: 17057362]
[http://dx.doi.org/10.1038/sj.emboj.7600385] [PMID: 15372072]
[http://dx.doi.org/10.1101/gad.1262504] [PMID: 15574589]
[http://dx.doi.org/10.1038/sj.emboj.7600491] [PMID: 15565168]
[http://dx.doi.org/10.1016/j.molcel.2010.03.013] [PMID: 20471939]
[http://dx.doi.org/10.1111/j.1463-1326.2009.01118.x] [PMID: 19817794]
[http://dx.doi.org/10.1126/science.1190809]
[http://dx.doi.org/10.1007/s11892-016-0724-8] [PMID: 26973290]
[http://dx.doi.org/10.1038/cdd.2014.112] [PMID: 25190144]
[http://dx.doi.org/10.1186/s12943-018-0765-5] [PMID: 29471827]
[http://dx.doi.org/10.1016/j.biochi.2011.06.017] [PMID: 21712066]
[http://dx.doi.org/10.1038/nature05983] [PMID: 17589500]
[http://dx.doi.org/10.1002/wrna.1284] [PMID: 25879954]
[http://dx.doi.org/10.1515/bmc-2014-0012] [PMID: 25372759]
[http://dx.doi.org/10.1016/j.canlet.2019.05.007] [PMID: 31078732]
[http://dx.doi.org/10.1038/ncb0309-228] [PMID: 19255566]
[http://dx.doi.org/10.1101/gad.1706508] [PMID: 19056895]
[http://dx.doi.org/10.1093/emboj/cdf476] [PMID: 12198168]
[http://dx.doi.org/10.1038/nature08025] [PMID: 19458619]
[http://dx.doi.org/10.1261/rna.1155108] [PMID: 18566191]
[http://dx.doi.org/10.1038/nsmb1041] [PMID: 16369484]
[http://dx.doi.org/10.1038/ncb1577] [PMID: 17435748]
[http://dx.doi.org/10.1016/j.devcel.2014.01.032] [PMID: 24636259]
[http://dx.doi.org/10.1126/science.1226191]
[http://dx.doi.org/10.1016/j.molcel.2011.09.012] [PMID: 22055188]
[http://dx.doi.org/10.1016/j.cell.2012.08.041] [PMID: 23063121]
[http://dx.doi.org/10.1016/j.molcel.2008.09.014] [PMID: 18951094]
[http://dx.doi.org/10.1261/rna.035501.112] [PMID: 23006623]
[http://dx.doi.org/10.1016/j.cell.2009.06.044] [PMID: 19804757]
[http://dx.doi.org/10.1038/nature08349] [PMID: 19734881]
[http://dx.doi.org/10.1038/nrm3838] [PMID: 25027649]
[http://dx.doi.org/10.1016/j.molcel.2011.04.015] [PMID: 21596313]
[http://dx.doi.org/10.1016/j.cell.2004.12.031] [PMID: 15652478]
[http://dx.doi.org/10.1016/j.cell.2006.07.031] [PMID: 16990141]
[http://dx.doi.org/10.1101/gad.1184404] [PMID: 15014042]
[http://dx.doi.org/10.1073/pnas.2008323117] [PMID: 32929008]
[http://dx.doi.org/10.1016/j.tibs.2012.08.003] [PMID: 22944280]
[http://dx.doi.org/10.1038/ncb1596] [PMID: 17486113]
[http://dx.doi.org/10.1073/pnas.0804549105] [PMID: 18663219]
[http://dx.doi.org/10.1016/j.bbrc.2009.09.061] [PMID: 19769940]
[http://dx.doi.org/10.1016/j.ymeth.2010.01.032] [PMID: 20146939]
[http://dx.doi.org/10.1055/s-2001-18576] [PMID: 11460565]
[http://dx.doi.org/10.1046/j.1365-2362.2001.00896.x] [PMID: 11737239]
[http://dx.doi.org/10.1016/j.cell.2010.11.040] [PMID: 21145450]
[http://dx.doi.org/10.1074/jbc.271.49.31372] [PMID: 8940145]
[http://dx.doi.org/10.1111/j.1432-1033.1980.tb06059.x] [PMID: 6249596]
[http://dx.doi.org/10.1111/j.1749-6632.2009.04019.x]
[http://dx.doi.org/10.1038/nature05861] [PMID: 17554339]
[http://dx.doi.org/10.1126/science.1072682] [PMID: 12471242]
[http://dx.doi.org/10.1002/wrna.1240] [PMID: 24944010]
[http://dx.doi.org/10.1371/journal.pone.0022839] [PMID: 21829658]
[http://dx.doi.org/10.1007/s11010-014-2170-8] [PMID: 25084986]
[http://dx.doi.org/10.1093/labmed/lmy033] [PMID: 30060033]
[http://dx.doi.org/10.1007/s10753-012-9467-0] [PMID: 22535496]
[PMID: 30880764]
[http://dx.doi.org/10.1002/mc.21864] [PMID: 22213236]
[http://dx.doi.org/10.3233/CBM-140431] [PMID: 25524940]
[http://dx.doi.org/10.1155/2015/625659] [PMID: 26078483]
[http://dx.doi.org/10.1016/j.ensci.2018.09.002] [PMID: 30255159]
[http://dx.doi.org/10.1093/nar/gkq575] [PMID: 20591823]
[http://dx.doi.org/10.3389/fnmol.2020.00090] [PMID: 32581706]
[http://dx.doi.org/10.1371/journal.pone.0030832] [PMID: 22363497]
[http://dx.doi.org/10.1038/nri2925] [PMID: 21233852]
[http://dx.doi.org/10.1371/journal.pone.0073272] [PMID: 24023848]
[http://dx.doi.org/10.1007/s00592-010-0226-0] [PMID: 20857148]
[http://dx.doi.org/10.1111/1440-1681.13147] [PMID: 31355469]
[http://dx.doi.org/10.1007/s11010-011-0727-3] [PMID: 21249428]
[http://dx.doi.org/10.1371/journal.pone.0115209] [PMID: 25500583]
[http://dx.doi.org/10.2337/db09-0881] [PMID: 20086228]
[http://dx.doi.org/10.1007/s11892-006-0031-x] [PMID: 16898568]
[http://dx.doi.org/10.3389/fendo.2018.00384]
[http://dx.doi.org/10.2337/db07-1252] [PMID: 18633110]
[http://dx.doi.org/10.1007/s00125-013-2993-y] [PMID: 23842730]
[http://dx.doi.org/10.1167/iovs.11-8992] [PMID: 22205611]
[http://dx.doi.org/10.1155/2018/6890501] [PMID: 29707000]
[http://dx.doi.org/10.1155/2017/4727942] [PMID: 28706953]
[http://dx.doi.org/10.1371/journal.pone.0084425] [PMID: 24376808]
[http://dx.doi.org/10.18632/oncotarget.8280] [PMID: 27015561]
[PMID: 23441115]
[http://dx.doi.org/10.1136/bjophthalmol-2015-306924] [PMID: 26541434]
[http://dx.doi.org/10.12659/MSM.890686] [PMID: 24743332]
[PMID: 35304162]
[http://dx.doi.org/10.2337/diabetes.50.12.2792] [PMID: 11723063]
[http://dx.doi.org/10.1167/iovs.10-6879] [PMID: 21498619]
[http://dx.doi.org/10.1167/iovs.13-13631] [PMID: 24985472]
[http://dx.doi.org/10.1167/iovs.16-21223] [PMID: 28297724]
[http://dx.doi.org/10.1155/2016/3958453] [PMID: 26997759]
[http://dx.doi.org/10.1016/j.visres.2017.03.009] [PMID: 28433754]
[http://dx.doi.org/10.1167/iovs.13-13076] [PMID: 24867582]
[http://dx.doi.org/10.1371/journal.pone.0114692] [PMID: 25490205]
[http://dx.doi.org/10.4239/wjd.v6.i3.432] [PMID: 25897354]
[http://dx.doi.org/10.1016/j.jpainsymman.2005.04.009] [PMID: 16256902]
[http://dx.doi.org/10.1016/j.jns.2006.03.011] [PMID: 16631800]
[http://dx.doi.org/10.1007/s11892-016-0727-5] [PMID: 26897744]
[http://dx.doi.org/10.1007/s13105-014-0378-4] [PMID: 25567745]
[http://dx.doi.org/10.1016/j.neuroscience.2013.11.057] [PMID: 24316060]
[http://dx.doi.org/10.2337/db16-1182] [PMID: 28899883]
[http://dx.doi.org/10.2147/DDDT.S157109] [PMID: 29398906]
[http://dx.doi.org/10.1016/j.tins.2004.11.002] [PMID: 15626495]
[http://dx.doi.org/10.1016/j.freeradbiomed.2010.12.006] [PMID: 21163346]
[http://dx.doi.org/10.1016/j.ijcard.2012.06.006] [PMID: 22748497]
[http://dx.doi.org/10.1172/JCI11916] [PMID: 11160145]
[http://dx.doi.org/10.2147/IJNRD.S40172] [PMID: 25342915]
[http://dx.doi.org/10.1016/j.kint.2016.02.042] [PMID: 27312444]
[http://dx.doi.org/10.1007/s12020-008-9114-6] [PMID: 18972226]
[http://dx.doi.org/10.1155/2011/304852] [PMID: 21694443]
[http://dx.doi.org/10.1186/1471-2369-15-142] [PMID: 25182190]
[http://dx.doi.org/10.1007/s11033-013-2763-4] [PMID: 24057185]
[http://dx.doi.org/10.1074/jbc.M116.753822] [PMID: 27913625]
[http://dx.doi.org/10.1681/ASN.2015010111] [PMID: 26647423]
[http://dx.doi.org/10.3892/mmr.2018.8407] [PMID: 29328400]
[http://dx.doi.org/10.1371/journal.pone.0173918] [PMID: 28301595]
[http://dx.doi.org/10.1155/2013/653789] [PMID: 23533715]
[http://dx.doi.org/10.2337/dc11-1682] [PMID: 22210568]
[http://dx.doi.org/10.1016/j.jchf.2014.08.004] [PMID: 25660838]
[http://dx.doi.org/10.1016/j.diabres.2013.10.011] [PMID: 24176244]
[http://dx.doi.org/10.1161/JAHA.112.000745] [PMID: 23316282]
[http://dx.doi.org/10.1002/emmm.201202318] [PMID: 23733368]
[http://dx.doi.org/10.4149/endo_2014_02_103] [PMID: 24824805]
[http://dx.doi.org/10.1016/j.yjmcc.2017.03.002] [PMID: 28279663]
[http://dx.doi.org/10.1155/2016/4285942] [PMID: 28050558]
[http://dx.doi.org/10.4149/BLL_2016_031] [PMID: 26925748]
[http://dx.doi.org/10.4149/BLL_2016_074] [PMID: 27546538]
[http://dx.doi.org/10.1155/2014/379537] [PMID: 25298619]