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Effect Of Mycophenolate Mofetil On Expression Of MicroRNAs In IgA Nephropathy Patients

Posted on:2015-07-07Degree:MasterType:Thesis
Country:ChinaCandidate:H F HuFull Text:PDF
GTID:2284330422988172Subject:Medical renal disease
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Objective To explore the serum levels of miRNAs and the effect of mycophenolatemofetil treatment on them in IgA nephropathy patients.Methods47patients treated with MMF as MMF group,33patients without anytreatment as IgAN group which matched with MMF treatment group,15healthyvolunteers as C group.13patients in IgAN group complete self-control study as forbefore and after MMF treatment group. To explore the serum levels of miRNAsthrough real-time PCR, and compare serum levels of miRNAs between the threegroups.Results As compared with C group, the serum levels of miR-141(P=0.000),miR-155(P=0.000), miR-200a(P=0.000), miR-429(P=0.004) are increased, andmiR-29a(P=0.000), miR-21(P=0.002), miR-16(P=0.000), miR-148b(P=0.000) aredecreased in IgAN group. Serum levels of miR-141, miR-155, miR-200b, miR-200cand miR-429inversely correlate with estimate glomerular filtrationrate(eGFR)(r=-0.398, P=0.024; r=-0.343,P=0.048; r=-0.403, p=0.020; r=-0.517,p=0.002; r=-0.350, p=0.046)in IgAN patients. Serum levels of miR-21, miR-29ainversely correlate with urinary protein excretion(r=-0.366,p=0.043;r=-0.375,p=0.038); serum levels of miR-141, miR-155, miR-200b, miR-429positively correlate with urinary protein excretion(r=0.452,P=0.014;r=0.347,P=0.046; r=0.413,p=0.021;r=0.371,p=0.040)in IgAN patients.Serum level of miR-29a inversely correlates with glomerulosclerosisproportion(r=-0.384,p=0.030); serum levels of miR-200b, miR-429positivelycorrelate with glomerulosclerosis proportion (r=0.377,p=0.034;r=0.337,p=0.047);serum level of miR-210inversely correlates with crescentproportion(r=-0.638,p=0.000) in IgAN patients. Serum level of miR-210positivelycorrelates with systolic blood pressure and diastolic blood pressure(r=0.389,p=0.034;r=0.487,p=0.008). As comparing Lee grade≤3with> Lee grade3patients, the serumlevels of miR-141, miR-192, miR-200a, miR-200b, miR-200c, miR-210, miR-429,miR-155are higher, and miR-16, miR-21, miR-148b, miR-29a are lower in the latter, but the differences are not statistically significant.The serum levels ofmiR-141(P=0.000), miR-155(P=0.045), miR-192(P=0.008), miR200a(P=0.000),miR200b(P=0.002), miR429(P=0.048) in MMF group are significantly lower, andmiR-29a is higher than IgAN group(P=0.030).There is no significantly diference ofserum levels of miR-16, miR-21, miR-148b, miR200c, miR-210between the twogroups. The serum levels of miR-141(P=0.000), miR-200a(P=0.008),miR-200b(P=0.048) in after MMF treatment group are significantly lower than beforeMMF treatment group. The serum levels of miR-429, miR-210, miR-155, miR-192have a downward trend; miR-29a, miR-148b, miR-21, miR-16have a upward trend,but the differences are not statistically significant.Conclusion The serum levels of miR-141, miR-155, miR-200a, miR-429aresignificantly elevated, and serum levels of miR-21, miR-16, miR-29a, miR-148b aredecreased in IgAN patients. Serum levels of miR-141, miR-155, miR-200b, miR-200cand miR-429increased is closely related to renal function decline. Serum levels ofmiR-21, miR-29a decreased is closely related to urinary protein excretion; serumlevels of miR-141, miR-155, miR-200b, miR-429increased is closely related tourinary protein excretion in IgAN patients. Serum level of miR-29a decreased isclosely related to glomerulosclerosis; and serum levels of miR-200b, miR-429increased is closely related to glomerulosclerosis in IgAN patients. Serum level ofmiR-210increased is closely related to blood pressure. So the serum levels ofmiR-155,miR-141,miR-200a,miR-429,miR-21,miR-16,miR-29a,miR-148bcan be considered as important indicators of progression of IgAN. MMF couldalleviate urinary protein, and make the serum levels of miR-141, miR-155, miR-192,miR-200a, miR-200b, miR-429reduced, miR-29a increased in IgAN patientssignificantly. Serum levels of miR-141, miR-155, miR-192, miR-200a, miR-200b,miR-429and miR-29a may be considered as therapeutic target, reflecting the effect ofMMF treat with IgAN. But the specific mechanism need further study. MMF do nothave any influences on serum levels of miR-16, miR-21, miR-148b, miR-200c,miR-210in IgAN patients. After verification through self-control study, comparedwith pre-treatment group, serum levels of miR-141, miR-200a, miR-200b aresignificantly reduced than after MMF treatment group,which consistent with thecross-sectional study. Objective To explore the urine levels of microRNAs and the effect of mycophenolatemofetil treatment on them in immunoglobulin A nephropathy(IgAN) patients.Methods47patients treated with MMF as MMF group,33patients without anytreatment as IgAN group which matched with MMF treatment group,15healthyvolunteers as C group.13patients in IgAN group complete self-control study as forbefore and after MMF treatment group. To explore the urine levels of miRNAsthrough real-time PCR, and compare urine levels of miRNAs between the threegroups.Results As compared with C group, the urine levels of miR-155(P=0.043),miR-192(P=0.046), miR-21(P=0.029), miR-148b(P=0.047) are increased, andmiR-200b(P=0.043), miR-29a(P=0.048), miR-429(P=0.042) are decreased inNIgAN group. Urine levels of miR-29a, miR-210positively correlateeGFR(r=0.398,p=0.023;r=0.365,p=0.046); miR-148b, miR-141inversely correlateswith eGFR(r=-0.349,p=0.047;r=-0.368,p=0.049)in IgAN patients. Urine levels ofmiR-29a, miR-200b, miR-200c, miR-429, miR-210inversely correlate with urinaryprotein excretion(r=-0.396,p=0.030; r=-0.435,p=0.016; r=-0.423, p=0.040;r=-0.441, p=0.015; r=-0.392,p=0.036). Urine levels of miR-29a, miR-200b,miR-200c, miR-429, miR-210inversely correlate with glomerulosclerosisproportion(r=-0.587, p=0.000;r=-0.537, p=0.002;r=-0.524, p=0.002;r=-0.550,p=0.001;r=-0.593, p=0.000) in IgAN patients. Urine levels of miR-429, miR-29ainversely correlate with diastolic blood pressure(r=-0.393,p=0.024;r=-0.481,p=0.005). As comparing Lee grade≤3with> Lee grade3patients, the urinelevels of miR-141, miR-155, miR-21, miR-192, miR-148b, miR-200a are higher, butthe differences are not statistically significant; and miR-29a, miR-16, miR-200b,miR-200c, miR-429, miR-210are lower in the latter, the differences ofmiR-29a(P=0.025), miR-200b (P=0.049), miR-429(P=0.021), miR-210(P=0.018)are statistically significant.The urine levels of miR-141(P=0.000),miR-200a(P=0.000) in MMF group are significantly lower, and miR-29a(P=0.032), miR-21(P=0.014), miR-192(P=0.008), miR-200b(P=0.011), miR-200c(P=0.005),miR-429(P=0.000) are higher than IgAN group.There is no significantly diference ofurine levels of miR-16, miR-210, miR-148b, miR-155between the two groups. Theurine level of miR-141(P=0.001) in after MMF treatment group are significantlylower than before MMF treatment group. The urine levels of miR-200a, miR-148bhave a downward trend, but the differences are not statistically significant. The urinelevel of miR-192(P=0.039) in after MMF treatment group are significantly higherthan before MMF treatment group. The urine levels of miR-29a, miR-210, miR-21,miR-16, miR-429, miR-200b, miR-200c have a upward trend, but the differences arenot statistically significant.Conclusion The urine levels of miR-155, miR-192, miR-21, miR-148b aresignificantly elevated, and urine levels of miR-200b, miR-29a, miR-429are decreasedin IgAN patients. Urine levels of miR-29a, miR-210decreased is closely related torenal function decline;miR-148b, miR-141increased is closely related to renalfunction decline in IgAN patients. Urine levels of miR-29a, miR-200b, miR-200c,miR-429, miR-210decreased is closely related to urinary protein excretion in IgANpatients. Urine levels of miR-29a, miR-200b, miR-200c, miR-429, miR-210decreased is closely related to glomerulosclerosis in IgAN patients. Urine levels ofmiR-429, miR-29a decreased is closely related to diastolic blood pressure in IgANpatients. With LEE grade increasing, urine levels of miR-29a, miR-200b, miR-429,miR-210decreased in IgAN patients. MMF could alleviate urinary protein, and makethe urine levels of miR-141, miR-200a reduced, miR-29a, miR-200b, miR-200c,miR-429increased in IgAN significantly. Urine levels of miR-141, miR-200a,miR-29a, miR-200b, miR-200c, miR-429may be considered as therapeutic target,reflecting the effect of MMF treat with IgAN. But the specific mechanism needfurther study. MMF do not has any influences on urine levels of miR-16, miR-210,miR-148b, miR-155in IgAN patients. After verification through self-control study,compared with pre-treatment group,urine level of miR-141is significantly reducedthan after MMF treatment group, which consistent with the cross-sectional study. Objective To explore the intra-renal levels of miRNAs and the relationship ofmiRNAs between serum, urine and intra-renal in immunoglobulin A nephropathypatients.Methods30patients with biopsy-proven IgA nephropathy as IgAN group,15patientswith nephrectomy for kidney cancer as controls. To explore the intra-renal levels ofmiRNAs through real-time PCR, and compare intra-renal levels of miRNAs betweenthe two groups. Moreover, to explore the relationship of miRNAs between serum,urine and intra-renal in IgAN patients.Results As compared with control group, the intra-renal level of miR-155is increased(P=0.000), and miR-141(P=0.000), miR-200a(P=0.000), miR-200b(P=0.000),miR-200c(P=0.000), miR-29a(P=0.000), miR-429(P=0.000) are decreased inIgAN group. Intra-renal levels of miR-192, miR-148b, miR-210positively correlatewith eGFR(r=0.484,p=0.002;r=0.474,p=0.007; r=0.426,p=0.019); miR-21, miR-155inversely correlate with eGFR(r=-0.541, p=0.047;r=-0.488,p=0.008)in IgANpatients. Intra-renal levels of miR-21, miR-429, miR-155positively correlate withurinary protein excretion(r=0.533,p=0.002; r=0.360,p=0.047;r=0.402,p=0.028);miR-148b、 miR-210inversely correlate with urinary proteinexcretion(r=-0.506,p=0.004;r=-0.418,p=0.021) in IgAN patients. Intra-renal levelsof miR-148b, miR-192inversely correlate with glomerulosclerosisproportion(r=-0.572,p=0.001;r=-0.455,p=0.012); miR-21, miR-429positivelycorrelate with crescent proportion(r=0.515,p=0.004;r=0.366,p=0.047); miR-210inversely correlates with crescent proportion(r=-0.492,p=0.006)in IgAN patients.Intra-renal levels of miR-21, miR-16positively correlate with systolic bloodpressure(r=0.353,p=0.048;r=0.490,p=0.006); miR-200a inversely correlates withsystolic blood pressure(r=-0.368,p=0.049); miR-16positively correlates withdiastolic blood pressure(r=0.358,p=0.045) in IgAN patients. As comparing Lee grade ≤3with> Lee grade3patients, the intra-renal levels of miR-141, miR-155, miR-21,miR-200b, miR-429, miR-16are higher, the difference of miR-21is statisticallysignificant(P=0.047); and miR-29a, miR-192, miR-210, miR-148b, miR-200a,miR-200c are lower in the latter, the differences of miR-192(P=0.004),miR-210(P=0.014), miR-148b(P=0.015) are statistically significant. Serum level ofmiR-141inversely correlates with intra-renal level of miR-141(r=-0.473,p=0.015);serum level of miR-155positively correlates with urine level ofmiR-155(r=0.639,p=0.000)in IgAN patients. Urine level of miR-29a positivelycorrelates with intra-renal level of miR-29a(r=0.360,p=0.048); serum level ofmiR-29a positively correlates with urine level of miR-29a(r=0.733,p=0.000) in IgANpatients. Serum level of miR-192positively correlates with urine level ofmiR-192(r=0.463,p=0.026) in IgAN patients. Serum level of miR-210positivelycorrelates with intra-renal level of miR-210(r=0.465,p=0.025) in IgAN patients. Thecorrelations between the other miRNAs are not statistically significant.Conclusion The intra-renal level of miR-155is significantly elevated, and intra-renallevels of miR-141, miR-200a, miR-200b, miR-200c, miR-29a, miR-429are decreasedin IgAN patients. Intra-renal levels of miR-192, miR-148b, decreased, and miR-155increased is closely relate to renal function decline in IgAN patients. Intra-renal levelsof miR-155increased, miR-148b decreased is closely relate to urinary proteinexcretionin IgAN patients. Intra-renal levels of miR-148b, miR-192decreased isclosely relate to glomerulosclerosis.Intra-renal levels of miR-16increased,andmiR-200a decreased is closely relate to blood pressure in IgAN patients. With LEEgrade increasing, intra-renal level of miR-21increased; miR-192, miR-210, miR-148bdecreased in IgAN patients..Serum level of miR-141increased accompanied byintra-renal level of miR-141decreased, serum level of miR-155increasedaccompanied by urine level of miR-155increased, urine level of miR-29a decreasedaccompanied by intra-renal level of miR-29a decreased, serum level of miR-29adecreased accompanied by urine level of miR-29a decreased, serum level of miR-192increased accompanied by urine level of miR-192increasedin IgAN patients. Theserum, urine and intra-renal levels of miRNAs interconnect each other, reflect theseverity of kidney injury together, but the expression of them is not alwaysconsistently each other. Objective To make the multiple linear regression analysis of related factors affectingprogress of IgA nephropathy, and to find the key factors affecting progress of IgAnephropathy.Methods30patients with biopsy-proven IgA nephropathy, collecting intra-renal,serum, urine specimens. To explore the intra-renal, serum, urine levels of miRNAsthrough real-time PCR, and collect relevant clinical and pathological datas, make themultiple linear regression analysis of all factors affecting proteinuria, renalfunction,blood pressure in IgA nephropathy patients.Results Urinary protein excretion hasa negative linear regression relationship withserum albumin(β=-0.367,p=0.008), has a positive linear regression relationshipwith crescent proportion, serum creatinine concentration, intra-renal miR-21(β=0.545,p=0.002;β=0.267,p=0.025;β=0.410,p=0.005) in IgA nephropathy patients. Serum creatinine concentration has a positive linear regression relationship withglomerulosclerosis proportion (β=0.627,p=0.000), has a positive linear regressionrelationship with intra-renal miR-21(β=0.459,p=0.001)in IgA nephropathy patients. eGFR has a positive linear regression relationship with intra-renal level of miR-192(β=0.401,p=0.003), has a negative linear regression relationship with intra-renalmiR-29a and LEE grade(β=-0.415,p=0.001;β=-0.481,p=0.001)in IgAnephropathy patients. Systolic blood pressure has a positive linear regressionrelationship with serum level of miR-200c,urine level of miR-210, hemoglobin,LEEgrade (β=0.343,p=0.009; β=0.305,p=0.011; β=0.352,p=0.004;β=0.380,p=0.005). Diastolic blood pressure has a positive linear regression relationshipwith hemoglobin,LEE grade (β=0.465,p=0.003;β=0.649,p=0.000), has anegative linear regression relationship with eGFR, intra-renal level of miR-429(β=-0.319,p=0.040;β=-0.389,p=0.004)in IgAnephropathy patients..Conclusion Intra-renal level of miR-21increased is the independent factor affecting serum creatinine concentration IgA nephropathy patients.Intra-renal level of miR-192decreased is the independent factors affecting eGFR in IgA nephropathy patients.Intra-renal level of miR-21increased is the independent factors affecting urinaryprotein excretion. Serum level of miR-200c, urine level of miR-210increased,are theindependent factors affecting systolic blood pressure in IgA nephropathy patients.intra-renal level of miR-429increased is the independent factors affecting diastolicblood pressure in IgA nephropathy patients.
Keywords/Search Tags:IgA Nephropathy, MicroRNAs, Mycophenolate MofetilImmunoglobulin A Nephropathy, GlomerulosclerosisCrescentIgA Nephropathy, Urinary Protein Excretion, SerumCreatinine Concentration, Multiple Linear Regression Analysis
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