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脾脏CD4^+T细胞组蛋白乙酰化修饰与NOD小鼠糖尿病肾病进展的关系 被引量:3

Relationship between histone acetylation modification in spleen CD4^+ T cells and diabetic nephropathy of nonobese diabetic mice
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摘要 目的探讨脾脏CD4^+T细胞组蛋白乙酰化修饰与非肥胖型糖尿病(NOD)小鼠糖尿病肾病发生及进展的关系。方法SPF级雌性NOD小鼠24只,8周龄,随机分为4组,检测12、18、24、30周龄小鼠的随机血糖,酶联免疫吸附测定(ELISA)试剂盒检测尿白蛋白和尿肌酐。分离脾脏CD4^+T细胞,H3、H4乙酰化试剂盒检测CIM^+T细胞H3、H4总体乙酰化水平,实时定量PCR检测组蛋白乙酰化相关修饰酶的mRNA水平,Western印迹法验证实时定量PCR筛选出的阳性基因。结果与12周龄NOD小鼠相比,24和30周龄鼠血糖升高[(18.1±6.3)、(20.7±7.5)mmol/L比(7.2±3.1)mmol/L],尿白蛋白/肌酐比值升高[(4.04±1.54)、(8.11±1.77)mg/g比(2.12±0.56)mg/g],脾脏CD4^+T细胞H3总体乙酰化水平降低[(0.068±0.023)、(0.043±0.017)比(0.127±0.036)],H4总体乙酰化水平降低[(0.058±0.022)、(0.041±0.019)比(0.082±0.032)],均P〈0.05。在组蛋白乙酰化修饰酶谱中,与12周龄NOD小鼠相比,24和30周龄鼠组蛋白乙酰转移酶P300的mRNA水平下降[(15.53±6.31)、(13.76±3.62)比(22.94±7.40)],P300/CBP相关因子(PCAF)的mRNA水平也降低[(3.21±0.81)、(2.74±0.36)比(5.31±0.73)],而HDAC5mRNA及蛋白表达水平升高(均P〈0.05)。24和30周龄中已发病的NOD小鼠H3(r=-0.590,P=0.043)、H4(r=-0.702,P=0.011)乙酰化水平与尿白蛋白/肌酐比值呈负相关,HDAC5表达水平与尿白蛋白/肌酐比值呈正相关(r=0.673,P=0.016)。结论随着NOD小鼠周龄及肾脏损伤的进展,其脾脏CD4^+T细胞总体H3、H4乙酰化水平降低,组蛋白去乙酰化酶HDAC5表达水平升高。CD4^+T细胞中HDAC5的异常升高与NOD小鼠肾脏损害相关。 Objective To explore the relationship between histone aeetylation modification in spleen CD4^+ T cells and diabetic nephropathy. Methods Non-obese diabetic (NOD) mice were randomly divided into 4 groups and random blood glucose at 12, 18, 24 and 30 weeks were detected. Urinary albumin and creatinine were detected by enzyme-linked immunosorbent assay (ELISA). The global acetylation levels of H3 and H4 in CD4^+T cells were measured by H3/H4 acetylation kit. The relevant mRNA expression level of histone acetylation modification enzymes was detected by real-time quantitative polymerase chain reaction (PCR) and the altered expression genes verified by Western blot. Results Compared with mice from 12 weeks, there were significant increases in blood glucose levels and urinary albumin/creatinine ratio (ACR) from 24 and 30 weeks ( glucose: ( 18. 1±6. 3 ) and (20. 7±7.5 ) vs (7.2±3.1 ) mmol/L, ACR: (4. 04±1. 54) and (8.11±1.77) vs (2. 12±0. 56)rag/g). Conversely, the global acetylation levels of H3(0.068 ±0.023 and 0.043 ±0.017 vs 0. 127±0.036) and H4 (0.058 ±0.022 and 0.041 ±0.019 vs 0. 082 ± 0. 032) in spleen CD4+ T cells from 24 and 30 weeks were obviously lower. The mRNA levels of such histone acetylases as P300 ( 15.53 ± 6. 31 and 13.76±3.62 vs 22. 94 ± 7.40 ) and P300/CBP- associated factor(PCAF) (3.21 ± 0. 81 and 2. 74 ± 0. 36 vs 5.31 ± 0.73 ) declined while the protein and mRNA of histone deacetylase 5 ( HDAC5 ) significantly increased from 24 and 30 weeks. All the above differences were statistically significant ( P 〈 0. 05 ). The levels of H3 ( r = - 0. 590, P = 0. 043 ) and H4 (r = -0. 702, P = 0. 011 )were negatively correlated with urinary ACR while HDAC5 level was positively correlated with urinary ACR from 24 and 30 weeks (r = 0. 673, P = 0. 016). Conclusions With aging and progression of nephropathy in NOD mice, the global aeetylation levels of H3 and I-I4 decrease while the expression level of HDAC5 increases in spleen CD4^+ T cell. And altered HDAC5 expression in spleen CD4^+ T cells is closely eorrelated with kidney damage in NOD mice.
出处 《中华医学杂志》 CAS CSCD 北大核心 2015年第14期1061-1065,共5页 National Medical Journal of China
基金 国家自然科学基金青年基金(81200580) 教育部博士点基金(20120162120090) 湖南省自然科学基金(14JJ3042) 中央高校青年教师助推专项(2012QNZT157) 湖南省发改委基金(湘发改高技[2013]1199)
关键词 小鼠 近交NOD 组蛋白脱乙酰基酶类 组蛋白乙酰化 尿白蛋白/肌酐比值 Mice, inbred NOD Histone deaeetylases Histone acetylation Urinary albumin/ ereatinine ratio
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参考文献18

  • 1侯粲,李一君,周智广.糖尿病表观遗传学研究进展[J].中华医学杂志,2009,89(10):715-717. 被引量:6
  • 2王燕飞,侯粲,苏欣,周智广.组蛋白乙酰化与糖尿病[J].中华内分泌代谢杂志,2014,30(2):167-170. 被引量:6
  • 3Wegner M,Neddermann D,Pioninska-Stolzmann M,et al.Role of epigenetic mechanisms in the development of chronic complications of diabetes[J].Diabetes Res Clin Pract,2014,105(2):164-175.
  • 4Reddy MA,Natarajan R.Epigenetics in diabetic kidney disease [J].J Am Soc Nephrol,2011,22(12):2182-2185.
  • 5Casteels K,Waer M,Bouillon R,et al.1,25-Dihydroxyvitamin D3 restores sensitivity to cyclophosphamide-induced apoptosis in non-obese diabetic(NOD)mice and protects against diabetes[J].Clin Exp Immunol,1998,112(2):181-187.
  • 6Reddy MA,Tak PJ,Natarajan R.Epigenetic modifications in the pathogenesis of diabetic nephropathy[J].Semin Nephrol,2013,33(4):341-353.
  • 7Kato M,Natarajan R.Diabetic nephropathy-emerging epigenetic mechanisms[J].Nat Rev Nephrol,2014,10(9):517-530.
  • 8Miao F,Chen Z,Genuth S,et al.Evaluating the role of epigenetic histone modifications in the metabolic memory of type I diabetes[J].Diabetes,2014,63(5):1748-1762.
  • 9Miao F,Chen Z,Zhang L,et al.Profiles of epigenetic histone post-translational modifications at type I diabetes susceptible genes[J].J Biol Chem,2012,287(20):16335-16345.
  • 10侯粲,赵明,李霞,李一君,蔺怡,陆前进,周智广.2型糖尿病患者肿瘤坏死因子α及环氧合酶2组蛋白H3乙酰化研究[J].中华医学杂志,2011,91(26):1805-1808. 被引量:5

二级参考文献73

  • 1Cave H, Polak M, Drunat S, et al. Refinement of the 6q chromosomal region implicated in transient neonatal diabetes. Diabetes, 2000, 49: 108-113.
  • 2Temple IK, Shield JP. Transient neonatal diabetes: a disorder of imprinting. J Med Genet, 2002, 39: 872-875.
  • 3Arima T, Drewell RA, Arney KL, et al. A conserved imprinting control region at the HYMAI/ZAC domain is implicated in transient neonatal diabetes mellitus. Hum Mol Genet, 2001, 10: 1475 -1483.
  • 4Mackay DJ, Coupe AM, Shield JP, et al. Relaxation of imprinted expression of ZAC and HYMAI in a patient with transient neonatal diabetes mellitus. Hum Genet, 2002, 110: 139-144.
  • 5Julier C, Hyer RN, Davies J, et al. Insulin-IGF2 region on chromosome llp encodes a gene implicated in HLA-DR4- dependent diabetes susceptibility. Nature, 1991, 354: 155-159.
  • 6Polychronakos C, Kukuvitis A. Parental genomic imprinting in endocrinopathies. Eur J Endocrinol, 2002, 147: 561-569.
  • 7McCann JA, Xu YQ, Frechette R, et al. The insulin-like growth factor-II receptor gene is associated with type 1 diabetes: evidence of a maternal effect. J Clin Endocrinol Metab, 2004, 89: 5700- 5706.
  • 8Wu W, Shang J, Feng Y, et al. Identification of glucose- dependant insulin secretion targets in pancreatic beta cells by combining defined-mechanism compound library screening and siRNA gene silencing. J Biomol Screen, 2008, 13 : 128-134.
  • 9Marzban L, Tomas A, Becker TC, et al. Small interfering RNA- mediated suppression of proislet amyloid polypeptide expression inhibits islet amyloid formation and enhances survival of human islets in culture. Diabetes, 2008, 57 : 3045-3055.
  • 10Poy MN, Eliasson L, Krutzfeldt J, et al . A pancreatic isletspecific microRNA regulates insulin secretion. Nature, 2004, 432 : 226-230.

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同被引文献29

  • 1Montserrat B Duran-Salgado,Alberto F Rubio-Guerra.Diabetic nephropathy and inflammation[J].World Journal of Diabetes,2014,5(3):393-398. 被引量:178
  • 2Zhang L, Wang F, Wang L, et al. Prevalence of chronic kidney disease in China: a cross-sectional survey [ J]. Lancet, 2012, 379 ( 9818 ) : 815-822. DOI: 10. 1016/S0140-6736 ( 12 ) 60033,6.
  • 3Thameem F, Kawalit IA, Adler SG, et al. Susceptibility gene search for nephropathy and related traits in Mexican-Americans [J]. Mol Biol Rep, 2013, 40(10): 5769-5779. DOI: 10. 1007/s11033-013-2680-6.
  • 4Sandholm N, MeKnight AJ, Salem RM, et al. Chromosome 2q31.1 associates with ESRD in women with type 1 diabetes[ J~. J Am Soe Nephrol, 2013, 24(10) : 1537-1543. DOI: 10. 1681/ ASN. 2012111122.
  • 5Byrne CD, Targher G. NAFLD: a muhisystem disease [ J ]. J Hepatol, 2015, 62(1 Suppl) : $47-$64. DOI: 10. lO16/j, jhep~ 2014.12. 012.
  • 6Fragoso A, Mendes F, Silva AP, et al. Insulin resistance as a predictor of cardiovascular morbidity and end-stage renal disease [ J]. J Diabetes Complications, 2015, 29(8) : 1098-1104. DOI: 10. lO16/j, jdiacomp. 2015.05. 010.
  • 7Bjornstad P, Cree-Green M, Baumgartner A, et al. Renal function is associated with peak exercise capacity in adolescents with type 1 diabetes[ J~. Diabetes care, 2015, 38( 1 ) : 126-131. DOI: 10. 2337/dc14-1742.
  • 8Ahmad J. Management of diabetic nephropathy: recent progress and future perspective[ J l. Diabetes Metab Syndr, 2015, 9 (4) : 343-358. DOI: 10. lO16/j, dsx. 2015.02. 008.
  • 9中华医学会糖尿病学分会微血管并发症学组.糖尿病肾病防治专家共识(2014年版)[J].中华糖尿病杂志,2014,6(11):792-801. 被引量:1487
  • 10楼灵通,叶英响,陈小弟.雷公藤多苷合补阳还五汤加味治疗糖尿病肾病52例观察[J].浙江中医杂志,2015,50(1):35-35. 被引量:3

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