miR-222调控多聚二磷酸腺苷核糖聚合酶-1在高糖致人肾系膜细胞外基质沉积中作用
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摘要
目的探讨miR-222调控多聚二磷酸腺苷(ADP)核糖聚合酶-1(PARP-1)在高糖致人肾系膜细胞外基质沉积中的作用。方法体外培养人肾系膜细胞株(HMC),使用高糖(25 m M)处理人肾系膜细胞,部分细胞应用miR-222抑制物或miR-222模拟物进行干预处理,Western blot检测PARP-1及FN蛋白表达。结果高糖培养组HMC在24 h时miR-222的表达上调,较对照组上调2.53倍,两组间比较,差异有统计学意义(P<0.05)。高糖+miR-222模拟物组HMC转染miR-222模拟物,可有效下调其靶蛋白PARP-1的表达,是高糖培养组的52.2%;高糖+miR-222抑制物组HMC转染miR-222抑制物,可有效上调其靶蛋白PARP-1的表达,较高糖培养组升高17.3%,两组间比较,差异均有统计学意义(P<0.05)。HMC细胞转染miR-222模拟物,可有效下调FN的表达,是高糖培养组的60.9%;而转染miR-222抑制物可有效上调纤维连接蛋白(FN)的表达,较高糖培养组升高18.8%,两组间比较,差异均有统计学意义(P<0.05)。结论 miR-222可通过调控PARP-1促进HMC基质增生。
Objective To investigate the effect of miR222 on the expression of ADP ribose polymerase-1( PARP-1) in extracellular matrix deposition of human renal mesangial cells induced by high glucose. Methods Human mesangial cells( HRMC) were cultured in vitro,HRMC were treated with high glucose( 25 m M). Some cells were treated with mir-222 inhibitor or mir-222 analogue. The expression of PARP-1 and FN protein were detected by Western blot. Results The expression of mir-222 was up-regulated by HMC in the high-sugar culture group in 24 hours,which was 2. 53 times higher than that in the control group( P < 0. 05). In high glucose + mir-222 analogue group,HMC transfected mir-222 analogue could effectively reduce the expression of its target protein PARP-1,which was52. 2% of the high-sugar culture group; in the high glucose + mir-222 inhibitory group,HMC transfection of mir-222 inhibitor could effectively increase the expression of the target protein PARP-1,and the higher glucose culture group increased 17. 3%( P < 0. 05).HMC cells transfected with mir-222 analogue can effectively reduce the expression of FN,which was 60. 9% of the high-sugar culture group; transfection of mir-222 inhibitor could effectively increase the expression of fibrinolytic protein( FN),and the higher glucose culture group increased 18. 8%,and the difference between the two groups was statistically significant( P < 0. 05). Conclusion The miR-222 regulates mesangial cell proliferation by regulating PARP.
Objective To investigate the effect of miR222 on the expression of ADP ribose polymerase-1( PARP-1) in extracellular matrix deposition of human renal mesangial cells induced by high glucose. Methods Human mesangial cells( HRMC) were cultured in vitro,HRMC were treated with high glucose( 25 m M). Some cells were treated with mir-222 inhibitor or mir-222 analogue. The expression of PARP-1 and FN protein were detected by Western blot. Results The expression of mir-222 was up-regulated by HMC in the high-sugar culture group in 24 hours,which was 2. 53 times higher than that in the control group( P < 0. 05). In high glucose + mir-222 analogue group,HMC transfected mir-222 analogue could effectively reduce the expression of its target protein PARP-1,which was52. 2% of the high-sugar culture group; in the high glucose + mir-222 inhibitory group,HMC transfection of mir-222 inhibitor could effectively increase the expression of the target protein PARP-1,and the higher glucose culture group increased 17. 3%( P < 0. 05).HMC cells transfected with mir-222 analogue can effectively reduce the expression of FN,which was 60. 9% of the high-sugar culture group; transfection of mir-222 inhibitor could effectively increase the expression of fibrinolytic protein( FN),and the higher glucose culture group increased 18. 8%,and the difference between the two groups was statistically significant( P < 0. 05). Conclusion The miR-222 regulates mesangial cell proliferation by regulating PARP.
引文
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[2]朱恒梅,祝胜郎,陈结慧,等.多聚二磷酸腺苷(ADP)核糖聚合酶-1介导高糖致大鼠肾脏系膜细胞t PA/PAI-1的紊乱[J].海南医学,2012,23(20):18-21.
[3]朱恒梅,祝胜郎,陈结慧,等.多聚二磷酸腺苷(ADP)核糖聚合酶-1(PARP-1)在高糖致大鼠肾脏系膜细胞细胞外基质沉积中的作用[J].中国医药导报,2012,9(31):8-11.
[4]Zhu H,Jiang Z,Lei P,et al.Poly(ADP-ribose)polymerase-1 mediates angiotensin II-induced expression of plasminogen activator inhibitor-1 and fibronectin in rat mesangial cells[J].Kidney Blood Press Res,2011,34(5):320-327.
[5]Lorenzen JM,Haller H,Thum T.MicroRNAs as mediators and therapeutic targets in chronic kidney disease[J].Nat Rev Nephrol,2011,7(5):286-294.
[6]Zhang DQ,Zhou CK,Jiang XW,et al.Increased expression of miR-222 is associated with poor prognosis in bladder cancer[J].World J Surg Oncol,2014,12:241.
[7]Shi Z,Zhao C,Guo X,et al.Differential expression of microRNAs in omental adipose tissue from gestational diabetes mellitus subjects reveals miR-222 as a regulator of ERαexpression in estrogen-induced insulin resistance[J].Endocrinology,2014,155(5):1982-1990.
[8]Neijenhuis S,Bajrami I,Miller R,et al.Identification of miRNA modulators to PARP inhibitor response[J].DNA Repair(Amst),2013,12(6):394-402.
[9]He HC,Han ZD,Dai QS,et al.Global analysis of the differentially expressed miRNAs of prostate cancer in Chinese patients[J].BMC Genomics,2013,14:757.
[10]Chen WX,Hu Q,Qiu MT,et al.miR-221/222:promising biomarkers for breast cancer[J].Tumour Biol,2013,34(3):1361-1370.
[11]Shi Z,Zhao C,Guo X,et al.Differential expression of microRNAs in omental adipose tissue from gestational diabetes mellitus subjects reveals miR-222 as a regulator of ER a expression in estrogen-induced insulin resistance[J].Endocrinology,2014,155(5):1982-1990.
[12]Zhu N,Zhang D,Chen S,et al.Endothelial enriched microRNAs regulate angiotensin II-induced endothelial inflammation and migration[J].Atherosclerosis,2011,215(2):286-293.
[13]Togliatto G,Trombetta A,Dentelli P,et al.Retraction Note to:MIR221/MIR222-driven post-transcriptional regulation of P27KIP1 and P57KIP2 is crucial for high-glucose-and AGE-mediated vascular cell damage[J].Diabetologia,2018.[Epub ahead of print]
[14]Liu X,Cheng Y,Yang J,et al.Cell-specific effects of miR-221/222 in vessels:molecular mechanism and therapeutic application[J].J Mol Cell Cardiol,2012,52(1):245-255.
[15]Li T,Yang GM,Zhu Y,et al.Diabetes and hyperlipidemia induce dysfunction of VSMCs:contribution of the metabolic inflammation/miRNA pathway[J].Am J Physiol Endocrinol Metab,2015,308(4):E257-E269.
[16]Cheng Y,Du L,Shi Q,et al.Identification of miR-221 and-222as important regulators in genotype IV swine hepatitis E virus ORF3-expressing HEK 293 cells[J].Virus Genes,2013,47(1):49-55.
[17]Kothapalli D,Castagnino P,Rader DJ,et al.Apolipoprotein Emediated cell cycle arrest linked to p27 and the Cox2-dependent repression of miR221/222[J].Atherosclerosis,2013,227(1):65-71.