1. bookVolume 51 (2017): Issue 3 (July 2017)
Journal Details
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Journal
eISSN
1336-0329
First Published
30 Mar 2016
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4 times per year
Languages
English
access type Open Access

Can regular moderate exercise lead to changes in miRNA-146a and its adapter proteins in the kidney of streptozotocin-induced diabetic male rats?

Published Online: 30 Aug 2017
Volume & Issue: Volume 51 (2017) - Issue 3 (July 2017)
Page range: 145 - 152
Journal Details
License
Format
Journal
eISSN
1336-0329
First Published
30 Mar 2016
Publication timeframe
4 times per year
Languages
English
Abstract

Objective. The aim of this study was to assess whether microRNA-146a and its adapter proteins TNF receptor associated factor6 (TRAF6) and interleukin-1 receptor-associated kinase-1 (IRAK1) may be changed in the kidney of streptozotocin-induced diabetic rats, following regular moderate exercise.

Methods. Forty adult male Wistar rats were allocated randomly into four groups (n=10), including sedentary control (SC), sedentary diabetic (SD), healthy sixty-day exercise (H60E), and diabetic sixty-day exercise (D60E) groups. Diabetes was induced by an intraperitoneal injection of 60 mg/kg streptozotocin. After 48 h, blood glucose levels >250 mg/dl was included to diabetic rats. After 2 days of diabetes induction, the exercise protocol began. Animals were exposed to 5 days of consecutive treadmill exercise for 60 min/day with the 22 m/min speed for 60 days. The kidneys of the rats were removed and microRNA was extracted from them using the miRCURYTM RNA isolation kit.

Results. In diabetic rats, statistical analysis revealed a significant decrease in miR-146a expression, non-significant decrease in IRAK1 mRNA expression, and non-significant increase in TRAF6 and NF-kB mRNA expression compared to the SC group. Exercise led to a non-significant increase in the expression of miR-146a and NF-kB mRNA in the kidneys of the diabetic group as compared to the SD group, significant increase in TRAF6 and IRAK1 mRNA expression compared to the H60E group, and significant increase in TRAF6 mRNA expression compared to the SD group.

Conclusion. The present data indicate that exercise might be able to help in the prevention in the diabetic nephropathy development.

Keywords

Alipour MR, Khamaneh AM, Yousefzadeh N, Mohammad-nejad D, Soufi FG. Upregulation of microRNA-146a was not accompanied by downregulation of pro-inflammatory markers in diabetic kidney. Mol Biol Rep 40, 6477–6683, 2013.10.1007/s11033-013-2763-424057185Search in Google Scholar

Asirvatham AJ, Magner WJ, Tomasi TB. miRNA regulation of cytokine genes. Cytokine 45, 58–69, 2009.10.1016/j.cyto.2008.11.010312985219121586Search in Google Scholar

Astrof S, Hynes RO. Fibronectins in vascular morphogenesis. Angiogenesis 12, 165–175, 2009.10.1007/s10456-009-9136-6271613819219555Search in Google Scholar

Atalay M, Oksala NK, Laaksonen DE, Khanna S, Nakao C, Lappalainen J, Roy S, Hanninen O, Sen CK. Exercise training modulates heat shock protein response in diabetic rats. J Appl Physiol 97, 605–611, 2004.10.1152/japplphysiol.01183.200315075301Search in Google Scholar

Balasubramanyam M, Aravind S, Gokulakrishnan K, Prabu P, Sathishkumar C, Ranjani H, Mohan V. Impaired miR-146a expression links subclinical inflammation and insulin resistance in Type 2 diabetes. Mol Cell Biochem 351, 197–205, 2011.10.1007/s11010-011-0727-321249428Search in Google Scholar

Banzet S, Chennaoui M, Girard O, Racinais S, Drogou C, Chalabi H, Koulmann N. Changes in circulating microRNAs levels with exercise modality. J Appl Physiol 115, 1237–1244, 2013.10.1152/japplphysiol.00075.201323950168Search in Google Scholar

Baxter D, McInnes IB, Kurowska-Stolarska M. Novel regulatory mechanisms in inflammatory arthritis: a role for microRNA. Immunol Cell Biol 90, 288–292, 2012.10.1038/icb.2011.11422249200Search in Google Scholar

Bhatt K, Lanting LL, Jia Y, Yadav S, Reddy MA, Magilnick N, Boldin M, Natarajan R. Anti-inflammatory role of microRNA-146a in the pathogenesis of diabetic nephropathy. J Am Soc Nephrol 27, 2277–2288, 2016.10.1681/ASN.2015010111497803426647423Search in Google Scholar

Biyashev D, Veliceasa D, Topczewski J, Topczewska JM, Mizgirev I, Vinokour E, Reddi AL, Licht JD, Revskoy SY, Volpert OV. miR-27b controls venous specification and tip cell fate. Blood 119, 2679–2687, 2012.10.1182/blood-2011-07-370635331128222207734Search in Google Scholar

Ceribelli A, Nahid MA, Satoh M, Chan EK. MicroRNAs in rheumatoid arthritis. FEBS Lett 585, 3667–3674, 2011.10.1016/j.febslet.2011.05.020316867721600203Search in Google Scholar

Chiasera JM, Ward-Cook KM, McCune SA, Wardlaw GM. Effect of aerobic training on diabetic nephropathy in a rat model of type 2 diabetes mellitus. Ann Clin Lab Sci 30, 346–353, 2000.Search in Google Scholar

Chen C. MicroRNAs as oncogenes and tumor suppressors. N Engl J Med 353, 1768, 2005.10.1056/NEJMp058190Search in Google Scholar

Chen H, Lan HY, Roukos DH, Cho WC. Application of microRNAs in diabetes mellitus. J Endocrinol 222, R1–R10, 2014.10.1530/JOE-13-0544Search in Google Scholar

Croce CM, Calin GA. miRNAs, cancer, and stem cell division. Cell 122, 6–7, 2005.10.1016/j.cell.2005.06.036Search in Google Scholar

Dogan A, Ergen N, Kurdak SS. The effects of regular aerobic exercise on renal functions in streptozotocin induced diabetic rats. J Sports Sci Med 9, 294–299, 2010.Search in Google Scholar

dos Santos Silva KA, da Silva Luiz R, Rampaso RR, de Abreu NP, Moreira ED, Mostarda CT, KD Angelis, de Paulo Castro Teixeira V, MC Irigoyen, N Schor. Previous exercise training has a beneficial effect on renal and cardiovascular function in a model of diabetes. PloS One 7, e48826, 2012.10.1371/journal.pone.0048826Search in Google Scholar

Fashi M, Agha-Alinejad H, Mahabadi HA, Rezaei B, Pakrad BB, Rezaei S. The effects of aerobic exercise on NF-κB and TNF-α in lung tissue of male rat. Novelty in Biomedicine 3, 131–134, 2015.Search in Google Scholar

Feng B, Chen S, McArthur K, Wu Y, Sen S, Ding Q, Feldman RD, Chakrabarti S. miR-146a–mediated extracellular matrix protein production in chronic diabetes complications. Diabetes 60, 2975–2984, 2011.10.2337/db11-0478Search in Google Scholar

Hayes C, Kriska A. Role of physical activity in diabetes management and prevention. J Am Diet Assoc 108, S19-S23, 2008.10.1016/j.jada.2008.01.016Search in Google Scholar

Horton E. Exercise and diabetes mellitus. Med Clin North Am 72, 1301–1321, 1988.10.1016/S0025-7125(16)30708-8Search in Google Scholar

Huang Y, Liu Y, Li L, Su B, Yang L, Fan W, Yin Q, Chen L, Cui T, Zhang J, Lu Y, Cheng J, Fu P, Liu F. Involvement of inflammation-related miR-155 and miR-146a in diabetic nephropathy: implications for glomerular endothelial injury. BMC nephrology 15, 142, 2014.10.1186/1471-2369-15-142423666325182190Search in Google Scholar

Ito D, Cao P, Kakihana T, Sato E, Suda C, Muroya Y, Ogaway, HU G, Ishii T, Ito O, Kohzuki M, Kiyomoto H. Chronic running exercise alleviates early progression of nephropathy with upregulation of nitric oxide synthases and suppression of glycation in Zucker diabetic rats. PloS One 10, e0138037, 2015.10.1371/journal.pone.0138037457495126379244Search in Google Scholar

Ji LL, Go mez-Cabrera MC, Steinhafel N, Vina J. Acute exercise activates nuclear factor (NF)-κB signaling pathway in rat skeletal muscle. FASEB J 18, 1499–1506, 2004.10.1096/fj.04-1846com15466358Search in Google Scholar

Lasser C, Eldh M, Lotvall J. Isolation and characterization of RNA-containing exosomes. JoVE 59, e3037, 2012.10.3791/3037Search in Google Scholar

Luis-Rodriguez D, Martinez-Castelao A, Gorriz JL, De-Alvaro F, Navarro-Gonzalez JF. Pathophysiological role and therapeutic implications of inflammation in diabetic nephropathy. World J Diabetes 3, 7–18, 2012.10.4239/wjd.v3.i1.7Search in Google Scholar

Ma Z, Qi J, Meng S, Wen B, Zhang J. Swimming exercise training-induced left ventricular hypertrophy involves microRNAs and synergistic regulation of the PI3K/AKT/mTOR signaling pathway. Eur J Appl Physiol 113, 2473–2486, 2013.10.1007/s00421-013-2685-9Search in Google Scholar

Matsuoka K, Nakao T, Atsumi Y, Takekoshi H. Exercise regimen for patients with diabetic nephropathy. J Diabet Complications 5, 98–100, 1991.10.1016/0891-6632(91)90032-KSearch in Google Scholar

McCarthy JJ, Esser KA. MicroRNA-1 and microRNA-133a expression are decreased during skeletal muscle hypertrophy. J Appl Physiol 102, 306–313, 2007.10.1152/japplphysiol.00932.200617008435Search in Google Scholar

Meisgen F, Landen NX, Wang A, Rethi B, Bouez C, Zuccolo M. MiR-146a negatively regulates TLR2-induced inflammatory responses in keratinocytes. J Invest Dermatol 134, 1931–1940, 2014.10.1038/jid.2014.8924670381Search in Google Scholar

Mogensen C, Christensen C, Vittinghus E. The stages in diabetic renal disease: with emphasis on the stage of incipient diabetic nephropathy. Diabetes 32(Suppl 2), 64–78, 1983.10.2337/diab.32.2.S646400670Search in Google Scholar

Moura J, Borsheim E, Carvalho E. The Role of MicroRNAs in Diabetic Complications—Special Emphasis on Wound Healing. Genes 5, 926–956, 2014.10.3390/genes5040926427692025268390Search in Google Scholar

Ozkaya YG, Agar A, Hacioglu G, Yargicoglu P. Exercise improves visual deficits tested by visual evoked potentials in streptozotocin-induced diabetic rats. Tohoku J Exp Med 213, 313–321, 2007.10.1620/tjem.213.31318075235Search in Google Scholar

Pankov R, Yamada KM. Fibronectin at a glance. J Cell Sci 115, 3861–3863, 2002.10.1242/jcs.0005912244123Search in Google Scholar

Pasquinelli AE. MicroRNAs and their targets: recognition, regulation and an emerging reciprocal relationship. Nat Rev Genet 13, 271–282, 2012.10.1038/nrg316222411466Search in Google Scholar

Peltier HJ, Latham GJ. Normalization of microRNA expression levels in quantitative RT-PCR assays: identification of suitable reference RNA targets in normal and cancerous human solid tissues. RNA 14, 844–852, 2008.10.1261/rna.939908232735218375788Search in Google Scholar

Poortmans JR, Mathieu N, De Plaen P. Influence of running different distances on renal glomerular and tubular impairment in humans. Eur J Appl Physiol Occup Physiol 72, 522–527, 1996.10.1007/BF002422858925826Search in Google Scholar

Praet S, van Loon L. Exercise: the brittle cornerstone of type 2 diabetes treatment. Diabetologia 51, 398–401, 2008.10.1007/s00125-007-0910-y266861318183362Search in Google Scholar

Radom-Aizik S, Zaldivar F, Oliver S, Galassetti P, Cooper DM. Evidence for microRNA involvement in exercise-associated neutrophil gene expression changes. J Appl Physiol 109, 252–261, 2010.10.1152/japplphysiol.01291.2009290419920110541Search in Google Scholar

Remuzzi G, Macia M, Ruggenenti P. Prevention and treatment of diabetic renal disease in type 2 diabetes: the BENEDICT study. J Am Soc Nephrol 17, S90–S97, 2006.10.1681/ASN.200512132416565256Search in Google Scholar

Rong Y, Bao W, Shan Z, Liu J, Yu X, Xia S, Gao H, Wang X, Yao P, Hu F, Liu L. Increased microRNA-146a levels in plasma of patients with newly diagnosed type 2 diabetes mellitus. PloS One 8, e73272, 2013.10.1371/journal.pone.0073272375944424023848Search in Google Scholar

Russell AP, Lamon S, Boon H, Wada S, Guller I, Brown EL, Chibalin AV, Zierath JR, Snow RJ, Stepto N, Wadley GD, Akimoto T. Regulation of miRNAs in human skeletal muscle following acute endurance exercise and short-term endurance training. J Physiol 591, 4637–4653, 2013.10.1113/jphysiol.2013.255695378420423798494Search in Google Scholar

Saba R, Sorensen DL, Booth SA. MicroRNA-146a: a dominant, negative regulator of the innate immune response. Front Immunol 5, 578, 2014.10.3389/fimmu.2014.00578424016425484882Search in Google Scholar

Safi SZ, Qvist R, Kumar S, Batumalaie K, Ismail IS. Molecular mechanisms of diabetic retinopathy, general preventive strategies, and novel therapeutic targets. Biomed Res Int 2014, 801269, 2014.10.1155/2014/801269410608025105142Search in Google Scholar

Taganov KD, Boldin MP, Chang KJ, Baltimore D. NF-κB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc Natl Acad Sci USA 103, 12481–12486, 2006.10.1073/pnas.0605298103Search in Google Scholar

Taylor RP, Ciccolo JT, Starnes JW. Effect of exercise training on the ability of the rat heart to tolerate hydrogen peroxide. Cardiovasc Res 58, 575–581, 2003.10.1016/S0008-6363(03)00285-2Search in Google Scholar

Tufescu A, Kanazawa M, Ishida A, Lu H, Sasaki Y, Ootaka T, Sato T, Kohzuki M. Combination of exercise and losartan enhances renoprotective and peripheral effects in spontaneously type 2 diabetes mellitus rats with nephropathy. J Hypertens 26, 312–321, 2008.10.1097/HJH.0b013e3282f2450b18192846Search in Google Scholar

Umpierrez G, Korytkowski M. Diabetic emergencies (mdash) ketoacidosis. hyperglycaemic hyperosmolar state and hypoglycaemia. Nat Rev Endocrinol 12, 222–232, 2016.10.1038/nrendo.2016.1526893262Search in Google Scholar

Virvidakis C, Loukas A, Mayopoulou-Symvoulidou D, Mountokalakis T. Renal responses to bicycle exercise in trained athletes: influence of exercise intensity. Int J Sports Med 7, 86–88, 1986.10.1055/s-2008-10257393710667Search in Google Scholar

Ward KM, Mahan JD, Sherman WM. Aerobic training and diabetic nephropathy in the obese Zucker rat. Ann Clin Lab Sc 24, 266–277, 1994.Search in Google Scholar

Zacharewicz E, Lamon S, Russell AP. MicroRNAs in skeletal muscle and their regulation with exercise, ageing, and disease. Front Physiol 4, 10.3389, 2013.10.3389/fphys.2013.00266378622324137130Search in Google Scholar

Xie Y-F, Shu R, Jiang SY, Liu DL, Ni J, Zhang XL. MicroRNA-146 inhibits pro-inflammatory cytokine secretion through IL-1 receptor-associated kinase 1 in human gingival fibroblasts. J Inflamm 10, 20, 2013.10.1186/1476-9255-10-20366016323680172Search in Google Scholar

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