儿童IgA肾病血清PDGF-BB与临床病理及预后的关系
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摘要
目的:IgA肾病(IgAN)是当今世界上最常见的原发性肾小球疾病。以往的观点认为IgA肾病预后良好,现已明确该病呈进展性,最终15%-40%的患者发展为终末肾病。通过肾脏穿刺病理检查,可了解肾脏病变程度及判断预后,但作为一种创伤性检查,仍具有一定的风险性。人们在开展肾穿刺的同时,也在寻找指导治疗及反映肾脏病理变化,提示预后的敏感指标。我们从临床角度出发,以血小板源生长因子-BB(platelet derived growth factor-BB, PDGF-BB)为指标,结合肾穿刺病理检查,对IgA肾病患儿进行研究,旨在达到以下目的:1、研究不同病理类型IgA肾病患儿血清PDGF-BB的变化规律。2、探讨血清血小板源生长因子在IgA肾病患儿诊断和评估预后中的临床应用价值。
方法:
30例患儿均施以肾活检术,按世界卫生组织1982年诊断标准确诊IgA肾病(根据临床表现和实验室检查排除其他继发性IgA肾病)。同期选择非IgA肾病患儿21例为对照组一,选健康儿童15例作为对照组二。各组间年龄,性别等组成无显著差异。所有患儿及对照组儿童均采集清晨空腹静脉血,静置离心,分离血清,应用酶联免疫吸附法(ELISA)定量测定血小板源生长因子-BB。并同时测定血BUN、Cr,24小时尿蛋白。IgA肾病组按WHO1982年分型标准分为五级:Ⅰ、Ⅱ、Ⅲ、Ⅳ、Ⅴ级(依据WHO分级标准分成3组,Ⅰ、Ⅱ级为轻度,Ⅲ、Ⅳ级为中度,Ⅴ级为重度)。IgA肾病组分别于治疗前和治疗后3月检测上述指标,按治疗效果分为无效组、部分缓解组、基本缓解组。另将IgA肾病组以有无高血压分为两组。所有数据采用SAS6.12软件进行统计学处理,统计方法为方差分析、t检验、直线回归相关分析,以P<0.05为显著性界限。
结果:
1 IgA肾病组血清PDGF-BB水平(869.16±200.73ng/l)明显高于非IgA肾病组(447.38±186.38ng/l),t=7.602, p<0.05。
2 IgA肾病组血清PDGF-BB水平(869.16±200.73ng/l)明显高于正常对照组(247.35±55.79ng/l ),t=11.712,p<0.05。
3 IgA肾病病理重度病变组4例,中度病变组16例,轻度病变组10例。重度病变组血清PDGF-BB水平(1214.44±91.48 ng/l)明显高于中度病变组(912.85±97.20ng/l), t=5.604,p<0.05;重度病变组血清PDGF-BB水平(1214.44±91.48 ng/l)明显高于轻度病变组(661.13±82.66ng/l), t=11.100,p<0.05);中度病变组血清PDGF-BB水平(912.85±97.20 ng/l)明显高于轻度病变组(661.13±82.66 ng/l),t=6.786,p<0.05。
4 IgA肾病组按治疗效果分为无效组、部分缓解组、基本缓解组。无效组:治疗前血清PDGF-BB水平(1147.74±129.99ng/l) ;治疗后血清PDGF-BB水平(949.17±93.92ng/l)。部分缓解组:治疗前血清PDGF-BB水平( 888.36±120.78ng/l),治疗后血清PDGF-BB水平(327.42±147.69ng/l)。基本缓解组:治疗前血清PDGF-BB水平(736.69±133.53ng/l),治疗后血清PDGF-BB水平(326.55±187.22ng/l)。
4.1无效组治疗前明显高于部分缓解组治疗前,t=4.046, p<0.05,明显高于基本缓解组治疗前,t=6.330,p<0.05,明显高于正常对照组,t=22.70, p<0.05;治疗后仍明显高于部分缓解组治疗后,t=9.188, p<0.05,明显高于基本缓解组治疗后,t=7.658,p<0.05,明显高于正常对照组t=21.348, p<0.05;治疗前与治疗后比较无显著性差异,t=3.621, p>0.05。
4.2部分缓解组治疗前明显高于基本缓解组治疗前,t=2.850, p<0.05,明显高于正常对照组,t=18.007, p<0.05;治疗后与基本缓解组治疗后比较无显著差异,t=0.012, p>0.05,与正常对照组比较无显著差异,t=1.921, p>0.05;治疗前明显高于治疗后t=18.655,p<0.05。4.3基本缓解组治疗前明显高于正常对照组,t=12.936, p<0.05,治疗后与正常对照组比较无显著差异,t=1.5675,p>0.05,治疗前明显高于治疗后t=8.554, p<0.05。
5 IgA肾病组按有无高血压分为高血压组和非高血压组,高血压组血清PDGF-BB(1114.74±115.89 ng/l)明显高于非高血压组(785.89±135.60ng/l),t=6.280, p<0.05。
6血PDGF-BB与24小时尿蛋白成正相关(r=0.6732)。
7 PDGF-BB与血尿素氮、肌酐均无相关性。
结论:
1 IgA肾病患儿血PDGF-BB高于非IgA肾病组,高于正常对照组。
2随着肾脏病理变化的加重,血PDGF-BB水平也逐渐升高,提示检测血PDGF-BB可以间接反映IgA肾病患儿肾脏病理损伤的严重程度。
3 IgA肾病患儿治疗无效组血清PDGF-BB高于缓解组,有高血压组高于无高血压组,随尿蛋白的加重血清PDGF-BB增高。
4通过动态监测血清PDGF-BB的变化可以早期预测治疗效果及对预后做出评估,为IgA肾病的诊断和治疗效果及评估预后提供了理论依据,为临床提供简便易行的检测方法。
Objective:IgAN is the most common kind of gromerular disease .In the past,it was thought to be a good prognosis, but now we find that it is evolutional and about 15-40% of it developed to ESRD.Renal disopsy has been an important technology for inspeciving the development of kidney,However,it has risk to a certainty as an invading examination.Some researchers are searching for the serum indicators,which can partly reflect renal pathology.To combines clinical cases with renal biopsy,by assaying transforming PDGF-BB in children with IgAN。The study purposes are as following .1.To investe the change of serum Platelet derived grouth factor in different renal pathology type in children with IgA nephropathy .2.To explore that if the level of serum PDGF-BBcan act as the predictors in estimating degree of illness and prognosis in children with IgA nephropathy.
Methods: 30 children who were proved to be IgA nephropathy by biopsy were studied.There were also 21 children with none- IgA nephropathy as control groupⅠand 15 heathy children control groupⅡ.There was no significant difference in age and sexual composition among each group.All children were taken in for making serum.Monoclonal ELISA detected PDGF-BB.Serum BUN,Cr and 24h urinary protein were measured. Acorrding patholgical degree constituted by WHO in 1982 the IgA nephropathy group divided into five degreesⅠ、Ⅱ、Ⅲ、Ⅳ、Ⅴ。(Ⅰ、Ⅱwere light patholoic chang group,Ⅲ、Ⅳwere moderate patholoic chang group,Ⅴwas severe patholoic chang group)The IgA nephropathy group respectively examined above indexe before treatment and after treated for 3 mongths,divided into complete remission group,part remission group and no response group according the therapy effect. The IgA nephropathy group divided into two groups according if having hypertension or not.Results were expressed as the mean±SD,data were analyzed using SAS program 6.12for windows software.Analysis of variance,t test,linear regression and analysis of linear correlation were used to compared mean valuses.AP Value less than 0.05 was considered statistically significant.
Results:1 The serum level of PDGF-BB in IgA nephropathy group were significantly higher than that in none- IgA nephropathy group ( 869.16±200.73 vs. 447.38±186.38ng/l t= 7.602 ,p<0.05)2 The serum level of PDG-BBF in IgA nephropathy group were significantly higher than that in natural conrol group(869.16±200.73 vs. 247.35±55.79ng/l t=11.712 ,p<0.05) 3 There were 4 cases in severe patholoec change group ,16 in moderate patholoec change group and 10 in light patholoec change group。The serum level of PDGF-BB in the severe patholoec change group were significantly higher than that of the moderate patholoec change group (1214.44±91.48 vs. 912.85±97.20ng/l,t=5.604,p<0.05); The serum level of PDGF-BB in the severe patholoec change group were significantly higher than that of the light patholoec change group ( 1214.44±91.48 vs. 661.13±82.66ng/l,t=11.100,p<0.05); The serum level of PDGF-BB in the moderate patholoec change group were significantly higher than that of the light patholoec change group(912.85±97.20 vs. 661.13±82.66ng/l,,t=6.786,p<0.05.)4 The IgA nephropathy divided into no response group,part remission group and complete remission group according the therapy effect.The serum level of PDGF-BB in the no response group : it is 1147.74±129.99ng/l before treatment and 949.17±93.92ng/l after treatment. The serum level of PDGF-BB in the part remission group : it is 888.36±120.78ng/l before treatment and 327.42±147.69ng/l after treatment. The serum level of PDGF-BB in the complete remission group : it is 736.69±133.53ng/l before treatment and326.55±187.22ng/l after treatment.The no response group is significantly higher than the part remission group(t=4.046,p<0.05,) , significantly higher than the complete remission group (t=6.330,p<0.05)and significantly higher than the control groupⅡ(t=22.70,p<0.05) before treatment.;The no response group is still significantly higher than the part remission group(t=9.188,p<0.05) ,significantly higher than the complete remission group (t=7.658,p<0.05) and significantly higher than the control groupⅡ( t=21.348,p<0.05 ) after treatment ; It was no significant difference in no response group after and before treatment(t=3.621 ,p>0.05). The part remission group was significantly higher than the clmplete remission group( t=2.850,p<0.05)and significantly higher than the control groupⅡ(t=18.0071,p<0.05) befor treatment. There was no significant difference between part remission group and clmplete remission group after treatment(t=0.0122 ,p>0.05). There was no significant difference between part remission group and the control groupⅡafter treatment (t=1.921,p>0.05).It was significantly higher before treatment than after treatmen(tt=18.6550,p<0.05).The clmplete remission group were significantly higher than control groupⅡbefore treatment(t=12.936,p<0.05), and after treatment there was no significant difference with the control groupⅡ(t=1.5675,p>0.05);, The clmplete remission group Before treatment were significantly higher than after treatment(t=8.554,p<0.05)。5 IgA nephropathy divided into two groups according if having hypertensive or not. The serum level of PDGF-BB of the hyper-tensive group was significant higher than that of no- hypertensive group(1114.74±115.89 ng/l vs. 785.89±135.60ng/l,t=6.280,p<0.05)。6There were positive correlation between PDGF-BB and 24h pro(r=0.6732).7The serum level of PDGF-BB did not correlate with BUN and Cr.
Conclusions: 1The serum level of PDGF-BB in children with IgA nephropathy is higher than that of none- IgA nephropathy and higher than that of nomal control group.2As the pathological sevevety increased in children with IgA nephropathy ,the level of PDGF-BB was raised,which implied the level of serum PDGF-BB might reflect damages of renal pathology indirectly.3The serum level of PDGF-BB in no response group was significantly higher than that of the remission group,The serum level of PDGF-BB in the group with hypertensive was significantly higher than that of the group with no- hypertensive. As the urinary protein was increased in children with IgA nephropathy,the level of PDGF-BB was raised.4 Monitoring the dynamic change of serum PDGF-BB can assess the effect and evaluate the prognosis of IgA nephropathy。It is an evidence to therapatic effect and prognosis,which was a simple ,convenient and not traumatic measurement maker.
方法:
30例患儿均施以肾活检术,按世界卫生组织1982年诊断标准确诊IgA肾病(根据临床表现和实验室检查排除其他继发性IgA肾病)。同期选择非IgA肾病患儿21例为对照组一,选健康儿童15例作为对照组二。各组间年龄,性别等组成无显著差异。所有患儿及对照组儿童均采集清晨空腹静脉血,静置离心,分离血清,应用酶联免疫吸附法(ELISA)定量测定血小板源生长因子-BB。并同时测定血BUN、Cr,24小时尿蛋白。IgA肾病组按WHO1982年分型标准分为五级:Ⅰ、Ⅱ、Ⅲ、Ⅳ、Ⅴ级(依据WHO分级标准分成3组,Ⅰ、Ⅱ级为轻度,Ⅲ、Ⅳ级为中度,Ⅴ级为重度)。IgA肾病组分别于治疗前和治疗后3月检测上述指标,按治疗效果分为无效组、部分缓解组、基本缓解组。另将IgA肾病组以有无高血压分为两组。所有数据采用SAS6.12软件进行统计学处理,统计方法为方差分析、t检验、直线回归相关分析,以P<0.05为显著性界限。
结果:
1 IgA肾病组血清PDGF-BB水平(869.16±200.73ng/l)明显高于非IgA肾病组(447.38±186.38ng/l),t=7.602, p<0.05。
2 IgA肾病组血清PDGF-BB水平(869.16±200.73ng/l)明显高于正常对照组(247.35±55.79ng/l ),t=11.712,p<0.05。
3 IgA肾病病理重度病变组4例,中度病变组16例,轻度病变组10例。重度病变组血清PDGF-BB水平(1214.44±91.48 ng/l)明显高于中度病变组(912.85±97.20ng/l), t=5.604,p<0.05;重度病变组血清PDGF-BB水平(1214.44±91.48 ng/l)明显高于轻度病变组(661.13±82.66ng/l), t=11.100,p<0.05);中度病变组血清PDGF-BB水平(912.85±97.20 ng/l)明显高于轻度病变组(661.13±82.66 ng/l),t=6.786,p<0.05。
4 IgA肾病组按治疗效果分为无效组、部分缓解组、基本缓解组。无效组:治疗前血清PDGF-BB水平(1147.74±129.99ng/l) ;治疗后血清PDGF-BB水平(949.17±93.92ng/l)。部分缓解组:治疗前血清PDGF-BB水平( 888.36±120.78ng/l),治疗后血清PDGF-BB水平(327.42±147.69ng/l)。基本缓解组:治疗前血清PDGF-BB水平(736.69±133.53ng/l),治疗后血清PDGF-BB水平(326.55±187.22ng/l)。
4.1无效组治疗前明显高于部分缓解组治疗前,t=4.046, p<0.05,明显高于基本缓解组治疗前,t=6.330,p<0.05,明显高于正常对照组,t=22.70, p<0.05;治疗后仍明显高于部分缓解组治疗后,t=9.188, p<0.05,明显高于基本缓解组治疗后,t=7.658,p<0.05,明显高于正常对照组t=21.348, p<0.05;治疗前与治疗后比较无显著性差异,t=3.621, p>0.05。
4.2部分缓解组治疗前明显高于基本缓解组治疗前,t=2.850, p<0.05,明显高于正常对照组,t=18.007, p<0.05;治疗后与基本缓解组治疗后比较无显著差异,t=0.012, p>0.05,与正常对照组比较无显著差异,t=1.921, p>0.05;治疗前明显高于治疗后t=18.655,p<0.05。4.3基本缓解组治疗前明显高于正常对照组,t=12.936, p<0.05,治疗后与正常对照组比较无显著差异,t=1.5675,p>0.05,治疗前明显高于治疗后t=8.554, p<0.05。
5 IgA肾病组按有无高血压分为高血压组和非高血压组,高血压组血清PDGF-BB(1114.74±115.89 ng/l)明显高于非高血压组(785.89±135.60ng/l),t=6.280, p<0.05。
6血PDGF-BB与24小时尿蛋白成正相关(r=0.6732)。
7 PDGF-BB与血尿素氮、肌酐均无相关性。
结论:
1 IgA肾病患儿血PDGF-BB高于非IgA肾病组,高于正常对照组。
2随着肾脏病理变化的加重,血PDGF-BB水平也逐渐升高,提示检测血PDGF-BB可以间接反映IgA肾病患儿肾脏病理损伤的严重程度。
3 IgA肾病患儿治疗无效组血清PDGF-BB高于缓解组,有高血压组高于无高血压组,随尿蛋白的加重血清PDGF-BB增高。
4通过动态监测血清PDGF-BB的变化可以早期预测治疗效果及对预后做出评估,为IgA肾病的诊断和治疗效果及评估预后提供了理论依据,为临床提供简便易行的检测方法。
Objective:IgAN is the most common kind of gromerular disease .In the past,it was thought to be a good prognosis, but now we find that it is evolutional and about 15-40% of it developed to ESRD.Renal disopsy has been an important technology for inspeciving the development of kidney,However,it has risk to a certainty as an invading examination.Some researchers are searching for the serum indicators,which can partly reflect renal pathology.To combines clinical cases with renal biopsy,by assaying transforming PDGF-BB in children with IgAN。The study purposes are as following .1.To investe the change of serum Platelet derived grouth factor in different renal pathology type in children with IgA nephropathy .2.To explore that if the level of serum PDGF-BBcan act as the predictors in estimating degree of illness and prognosis in children with IgA nephropathy.
Methods: 30 children who were proved to be IgA nephropathy by biopsy were studied.There were also 21 children with none- IgA nephropathy as control groupⅠand 15 heathy children control groupⅡ.There was no significant difference in age and sexual composition among each group.All children were taken in for making serum.Monoclonal ELISA detected PDGF-BB.Serum BUN,Cr and 24h urinary protein were measured. Acorrding patholgical degree constituted by WHO in 1982 the IgA nephropathy group divided into five degreesⅠ、Ⅱ、Ⅲ、Ⅳ、Ⅴ。(Ⅰ、Ⅱwere light patholoic chang group,Ⅲ、Ⅳwere moderate patholoic chang group,Ⅴwas severe patholoic chang group)The IgA nephropathy group respectively examined above indexe before treatment and after treated for 3 mongths,divided into complete remission group,part remission group and no response group according the therapy effect. The IgA nephropathy group divided into two groups according if having hypertension or not.Results were expressed as the mean±SD,data were analyzed using SAS program 6.12for windows software.Analysis of variance,t test,linear regression and analysis of linear correlation were used to compared mean valuses.AP Value less than 0.05 was considered statistically significant.
Results:1 The serum level of PDGF-BB in IgA nephropathy group were significantly higher than that in none- IgA nephropathy group ( 869.16±200.73 vs. 447.38±186.38ng/l t= 7.602 ,p<0.05)2 The serum level of PDG-BBF in IgA nephropathy group were significantly higher than that in natural conrol group(869.16±200.73 vs. 247.35±55.79ng/l t=11.712 ,p<0.05) 3 There were 4 cases in severe patholoec change group ,16 in moderate patholoec change group and 10 in light patholoec change group。The serum level of PDGF-BB in the severe patholoec change group were significantly higher than that of the moderate patholoec change group (1214.44±91.48 vs. 912.85±97.20ng/l,t=5.604,p<0.05); The serum level of PDGF-BB in the severe patholoec change group were significantly higher than that of the light patholoec change group ( 1214.44±91.48 vs. 661.13±82.66ng/l,t=11.100,p<0.05); The serum level of PDGF-BB in the moderate patholoec change group were significantly higher than that of the light patholoec change group(912.85±97.20 vs. 661.13±82.66ng/l,,t=6.786,p<0.05.)4 The IgA nephropathy divided into no response group,part remission group and complete remission group according the therapy effect.The serum level of PDGF-BB in the no response group : it is 1147.74±129.99ng/l before treatment and 949.17±93.92ng/l after treatment. The serum level of PDGF-BB in the part remission group : it is 888.36±120.78ng/l before treatment and 327.42±147.69ng/l after treatment. The serum level of PDGF-BB in the complete remission group : it is 736.69±133.53ng/l before treatment and326.55±187.22ng/l after treatment.The no response group is significantly higher than the part remission group(t=4.046,p<0.05,) , significantly higher than the complete remission group (t=6.330,p<0.05)and significantly higher than the control groupⅡ(t=22.70,p<0.05) before treatment.;The no response group is still significantly higher than the part remission group(t=9.188,p<0.05) ,significantly higher than the complete remission group (t=7.658,p<0.05) and significantly higher than the control groupⅡ( t=21.348,p<0.05 ) after treatment ; It was no significant difference in no response group after and before treatment(t=3.621 ,p>0.05). The part remission group was significantly higher than the clmplete remission group( t=2.850,p<0.05)and significantly higher than the control groupⅡ(t=18.0071,p<0.05) befor treatment. There was no significant difference between part remission group and clmplete remission group after treatment(t=0.0122 ,p>0.05). There was no significant difference between part remission group and the control groupⅡafter treatment (t=1.921,p>0.05).It was significantly higher before treatment than after treatmen(tt=18.6550,p<0.05).The clmplete remission group were significantly higher than control groupⅡbefore treatment(t=12.936,p<0.05), and after treatment there was no significant difference with the control groupⅡ(t=1.5675,p>0.05);, The clmplete remission group Before treatment were significantly higher than after treatment(t=8.554,p<0.05)。5 IgA nephropathy divided into two groups according if having hypertensive or not. The serum level of PDGF-BB of the hyper-tensive group was significant higher than that of no- hypertensive group(1114.74±115.89 ng/l vs. 785.89±135.60ng/l,t=6.280,p<0.05)。6There were positive correlation between PDGF-BB and 24h pro(r=0.6732).7The serum level of PDGF-BB did not correlate with BUN and Cr.
Conclusions: 1The serum level of PDGF-BB in children with IgA nephropathy is higher than that of none- IgA nephropathy and higher than that of nomal control group.2As the pathological sevevety increased in children with IgA nephropathy ,the level of PDGF-BB was raised,which implied the level of serum PDGF-BB might reflect damages of renal pathology indirectly.3The serum level of PDGF-BB in no response group was significantly higher than that of the remission group,The serum level of PDGF-BB in the group with hypertensive was significantly higher than that of the group with no- hypertensive. As the urinary protein was increased in children with IgA nephropathy,the level of PDGF-BB was raised.4 Monitoring the dynamic change of serum PDGF-BB can assess the effect and evaluate the prognosis of IgA nephropathy。It is an evidence to therapatic effect and prognosis,which was a simple ,convenient and not traumatic measurement maker.
引文
1 Johnson RJ, Feehally J . Comprehensiv Clinical Nephrology. Ondon, Mosby, 2000, 26(5):1~10
2 AppelGB andGlassockRJ. IgA nephropathy. Neph SAP, 2002, 1(1):11~19
3 Ostendorf T, KunterU. The effects of platelet-derived growth factor inexperimental glomerulonephritis are independent of the transforming growth factor-beta system.J Am Soc Nephrol, 2002, 13(3), 658~667
4 Ooi BS, Cohen DJ, Veis JH. Biology of the mesangial cell in glomerulonephritis-role of cytokines. Proc Soc Exp Biol Med, 1996, 1(1):213~230
5 Matsuda M, Shiraaata K, Makino H, et al. Gene expression of PDGF and PDGF receptor in various forms of glomerulonephritis. Am J Nephrol, 1997, 17(1):25
6 Gesualdo L, Pinzani M, Floriano JJ, et al. Platelet- derived growth factor expression in mesangial proliferative glomeru- lonephritis. Lab Invest, 1991,(2): 65~76
7 郑丰,刘志红,周虹,等.血小板源生长因子在活动性狼疮性肾炎肾小球病理改变的作用.中华内科杂志, 1996, 35(9):601
8 Yoshimura A, Inui K, Suzuki T, et al. J Am Soc Nephrol, 1993;4:692
9 Matsuda M, Shilata K, Makino H, et al. Am J Nephrol, 1997, 17(1):25~31
10 Abboud HE. Kidney Int, 1993, 43:252~257
11 Fellstrom B, Klareskog L, Heldin CH et al. Kidney Int, 1989, 36:1099~1102
12 Taneda S, Hudkins KL, et al. Growth factor expression in a murine modelof cryoglobulinemia.Kidney Int, 2003, 63(2):576~590
13 Makino H, Sugiyama H, Kashihara N. Apoptosis and extracellular matrix-cell interactions in kidney disease. Kidney Int Suppl, 2000, 77:67~75
14 Mackensen HS, Bohle A, Christensen J, et al. ClinNephrol, 1992, 37:70~77
15 Ng YY, Huang TP, Wang Wc, et al. Tubular epithelial-Myofibroblast transdifferentiation in progressive tubulointerstitial fibrosis in 5/6 nephre-cotomized rats.Kidney Int, 1998, 54:864~870
16 Frank J, Engler-BlumG, RodemannHP, et al. Human renal tubular cells as a cytokine source:PDGF-B, GM-CSF and IL-6 mRNA expression in vitro. Experimental Nephrology, 1993, 1(1):26~35
17 Tang WW, Ulich TR, Lacey DL, et al. Platelet derived growth factor-BB induces renal interstitial myofibroblast formation and tubulointerstitial fi-brosis. AM J Pathology, 1996, 148(4):1169~1180
18 Yoshimura A, Inui K, Suzuki T, et al. Soc Nephrol, 1993,4:692
19 Frank J, Engler-BlumG, RodemannHP, et al. Human renal tubular cellsas a cytokine source: PDGF-B, GM-CSF and IL-6 mRNA expressionin vitro. Experimental Nephrology, 1993, 1(1):26~35
20 Lida H, Seifert R, Alpers CE, et al. Proc Natl Acad Sci USA, 1991, 88:6560~6564
21 Razzaque MS, Cheng M, Tagouchi T. J Comp Pathol, 1996, 114(2):175~182
22 Descamps-LatschaB, W itko-SarsatV, Nguyen-Khoa T, et al Earlyprediction of IgA nephropathy progression: proteinuriaand AOPP are strong prognosticmarkers. Kidney Int, 2004, 66(4):1606~1612
23 Lee HS, Lee MS, Lee SM, et a.l Histological grading of IgA ne-phropathy predicting renal outcome: revisitingH. S. Lees glomeru-largrading system. Nephrol Dial Transplant, 2005, 20(2):342~348
1 Eitner F, Ostendorf T, et al. PDGF-C expression in the developing and normal human kidney and in glomerular diseases. J Am Soc Nephrol, 2003, 14(5):1145~1153
2 Changsirikulchai S, Hudkins KL, et al.Platelet-derived growth factor-D ex-pression in developing and mature human kidneys.Kidney Int, 2002, (6) :2043~2054
3 Hiebsch RR, Raub TJ, Wattenberg BW et al. J Biol Chem, 1991, 266:20323~20337
4 Kanakaraj P, Raj S, Khan SA et al. M Biochemistry, 1991, 30:1761~1767
5 Ostendorf T, KunterU, et al. The effects of platelet-derived growth factor inexperimental glomerulonephritis are independent of the transforming growthfactor-beta system. J Am Soc Nephrol, 2002, 13(3), 658~667
6 Ostendorf Tammo, van Roeyen, Claudia RC, et al. A fully human monoclonalantibody(CR002) identifies PDGF-D as a novel mediator of mesangioprolerative glomerulonephritis. Journal of the American Society of Nephrology, 2003, 14(9):2237~224
7 PawsonT, ScottJD. Signaling throughs caffold, anchoring, andadaptor proteins. Science, 1997, 278:2075~2080
8 Cartel NJ, Liu J. PDGF-BB-mediated activation of p42(MAPK) is independent of PDGF beta-receptor tyrosine phosphorylation. Am J Physiol LungCell Mol Physiol, 2001,281(4):L786~798
9 Jacob A, Molkentin JD, et al. Insulin inhibits PDGF-directed VSMC migration via NO/cGMP increase of MKP-1 and its inactivation of MAPKs.Am JPhysiol Cell Physiol, 2002, 283(3):4~13
10 Houdhury GG. Akt serine threonine kinase regulates platelet-derived growthfactor-induced DNA synthesis in glomerular mesangial cells: regulation ofAND p27(kip1) gene expression. J Biol Chem, 2001, 276(38), 35636~35643
11 Yu Y, Sweeney M, Zhang S, et al. PDGF stimulates pulmonary vascularsmooth muscle cell proliferation by upregulating TRPC6 expression.Am JPhysiol Cell Physiol, 2003, 284(2):316~330
12 Wang SN, Hirschberg R. Growth factor ultrafiltration in experimental diabetic nephropathy contributes to interstitial fibrosis. American Journal of Physiology Renal Electrolyte Physiology, 2000, 278(4):554~560
13 KingsleyK, RustWL, et al. PDGF-BB enhances expression of,and reducesadhesion to, laminin-5 in vascular smooth muscle cells. Biochem BiophysRes Commun, 2002, 294(5):1017~1022
14 Enter F, Ostendorf T, Van Roeyen C, et al. Expression of a novel PDGFisform, PDGF-C, in normal and diseased rat kidney. J Am Soc Nephrol. 2002, 13(4):910~917
15 Changsirikulchai S, Hudkins KL, et al. Platelet-derived growth factor-D expression in developing and mature humankidney. Kidney Int. 2002, 62(6):2043~2054
16 Gesualdo L, Pinzani M, Floriano JJ, et al. Lab Invest, 1991, 65:160~167
17 Terada Y, Yamada T, Nakashima O, et al. J Am Soc Nephrol, 1997, 8(5):817~819
18 Yoshimura A, Inui K, Suzuki T, et al. J Am Soc Nephrol, 1993, 4:692
19 Frank J, Engler-BlumG, RodemannHP, et al. Human renal tubular cellsas a cytokine source: PDGF-B, GM-CSF and IL-6 mRNA expressionin vitro. Experimental Nephrology, 1993, 1(1):26~35
20 Winson WT, Thomas RU, David LL et al. American Journal of Pathology, 1996, 148(4): 1169~1180
21 Gesualdo L Pinzani M, Floriano JJ et al. Lab Invest, 1991, 65:160~164
22 Fellstrom B, Klareskog L, Heldin CH et al. Kidney Int, 1989, 36:1099~1102
23 Taneda S, Hudkins KL, et al. Growth factor expression in a murine modelof cryoglobulinemia. Kidney Int, 2003, 63(2):576~590
24 Makino H, Sugiyama H, Kashihara N. Apoptosis and extracellular matrix-cell interactions in kidney disease. Kidney Int Suppl, 2000, 77:67~75
25 Paul-RV, Wackym-PS, Budisavljevic-MN. J Am Soc Nephrol, 1998, 9(1):26~32
26 Lida H,Seifert R, Alpers CE, et al. Proc Natl Acad Sci USA,1991, 88:6560~6564
27 Razzaque MS, Cheng M, Tagouchi T. J Comp Pathol, 1996, 114(2):175~182
28 Yoshimura A, Inui K, Suzuki T, et al. J Am Soc Nephrol, 1993, 4:692
29 Matsuda M, Shilata K, Makino H, et al. Am J Nephrol, 1997, 17(1):25~31
30 Abboud HE. Kidney Int, 1993, 43:252~257
31 Mackensen HS, Bohle A, Christensen J, et al. ClinNephrol, 1992, 37:70~77
32 Knecht A, Fine LG, Kleinmn KS, et al. Am J Physiol, 1991, 261:292~299
33 Lonnemann G, Miller GA, Koch KM. J Am Soc Nephrol, 1994, 755:756
34 Frank J,Engler-BlumG,RodemannHP,et al.Human renal tubular cellsas a cytokine source:PDGF-B,GM-CSF and IL-6 mRNA expression in vitro.Experimental Nephrology,1993,1(1):26~35
35 Tang WW, Ulich TR, Lacey DL, et al. Platelet derived growth factor-BB induces renal interstitial myofibroblast formation and tubulointerstitial fibrosis. AM J Pathology, 1996, 148(4):1169~1180
36 Ng YY, Huang TP, Wang Wc, et al. Tubular epithelial-Myofibroblast transdifferentiation in progressive tubulointerstitial fibrosis in 5/6 nephre-cotomized rats. Kidney Int, 1998, 54:864~876
37 Wang SN, Hirschberg R. Growth Factor ultrafiltration in experimental dia-betic nephropathy contributes to interstitial fibrosis. American Journal of Physiology Renal Electrolyte Physiology, 2002, 278(4):554~560
38 Floege, Jurgen, Eitner, et al. PDGF-D and renal disease:Yet Another One of Those Growth Factors, J Am Soc Nephrol, 2003, 14(10):2690~2691
39 Tang WW. PDGF-BB induces renal tubulointerstitial Myofibroblast formation and tubulointerstitial fibrosis. Am J Pathol, 1996, 148(4):1169~1180
40 Li X, Ponten A, Aase K, et al. PDGF-C is a new protease-activated lIgAnd for the PDGF alpha-receptor. Nat Cell Biol, 2002, 2:302~309
41 Taneda, Sekiko, Hudkins, et al. Obstructive Uropathy in Mice and humans: Potential role for PDGF-D in the Progression of Tubulointerstitial Injury. J Am Soc Nephrol, 2003, 14(10):2544~2555
2 AppelGB andGlassockRJ. IgA nephropathy. Neph SAP, 2002, 1(1):11~19
3 Ostendorf T, KunterU. The effects of platelet-derived growth factor inexperimental glomerulonephritis are independent of the transforming growth factor-beta system.J Am Soc Nephrol, 2002, 13(3), 658~667
4 Ooi BS, Cohen DJ, Veis JH. Biology of the mesangial cell in glomerulonephritis-role of cytokines. Proc Soc Exp Biol Med, 1996, 1(1):213~230
5 Matsuda M, Shiraaata K, Makino H, et al. Gene expression of PDGF and PDGF receptor in various forms of glomerulonephritis. Am J Nephrol, 1997, 17(1):25
6 Gesualdo L, Pinzani M, Floriano JJ, et al. Platelet- derived growth factor expression in mesangial proliferative glomeru- lonephritis. Lab Invest, 1991,(2): 65~76
7 郑丰,刘志红,周虹,等.血小板源生长因子在活动性狼疮性肾炎肾小球病理改变的作用.中华内科杂志, 1996, 35(9):601
8 Yoshimura A, Inui K, Suzuki T, et al. J Am Soc Nephrol, 1993;4:692
9 Matsuda M, Shilata K, Makino H, et al. Am J Nephrol, 1997, 17(1):25~31
10 Abboud HE. Kidney Int, 1993, 43:252~257
11 Fellstrom B, Klareskog L, Heldin CH et al. Kidney Int, 1989, 36:1099~1102
12 Taneda S, Hudkins KL, et al. Growth factor expression in a murine modelof cryoglobulinemia.Kidney Int, 2003, 63(2):576~590
13 Makino H, Sugiyama H, Kashihara N. Apoptosis and extracellular matrix-cell interactions in kidney disease. Kidney Int Suppl, 2000, 77:67~75
14 Mackensen HS, Bohle A, Christensen J, et al. ClinNephrol, 1992, 37:70~77
15 Ng YY, Huang TP, Wang Wc, et al. Tubular epithelial-Myofibroblast transdifferentiation in progressive tubulointerstitial fibrosis in 5/6 nephre-cotomized rats.Kidney Int, 1998, 54:864~870
16 Frank J, Engler-BlumG, RodemannHP, et al. Human renal tubular cells as a cytokine source:PDGF-B, GM-CSF and IL-6 mRNA expression in vitro. Experimental Nephrology, 1993, 1(1):26~35
17 Tang WW, Ulich TR, Lacey DL, et al. Platelet derived growth factor-BB induces renal interstitial myofibroblast formation and tubulointerstitial fi-brosis. AM J Pathology, 1996, 148(4):1169~1180
18 Yoshimura A, Inui K, Suzuki T, et al. Soc Nephrol, 1993,4:692
19 Frank J, Engler-BlumG, RodemannHP, et al. Human renal tubular cellsas a cytokine source: PDGF-B, GM-CSF and IL-6 mRNA expressionin vitro. Experimental Nephrology, 1993, 1(1):26~35
20 Lida H, Seifert R, Alpers CE, et al. Proc Natl Acad Sci USA, 1991, 88:6560~6564
21 Razzaque MS, Cheng M, Tagouchi T. J Comp Pathol, 1996, 114(2):175~182
22 Descamps-LatschaB, W itko-SarsatV, Nguyen-Khoa T, et al Earlyprediction of IgA nephropathy progression: proteinuriaand AOPP are strong prognosticmarkers. Kidney Int, 2004, 66(4):1606~1612
23 Lee HS, Lee MS, Lee SM, et a.l Histological grading of IgA ne-phropathy predicting renal outcome: revisitingH. S. Lees glomeru-largrading system. Nephrol Dial Transplant, 2005, 20(2):342~348
1 Eitner F, Ostendorf T, et al. PDGF-C expression in the developing and normal human kidney and in glomerular diseases. J Am Soc Nephrol, 2003, 14(5):1145~1153
2 Changsirikulchai S, Hudkins KL, et al.Platelet-derived growth factor-D ex-pression in developing and mature human kidneys.Kidney Int, 2002, (6) :2043~2054
3 Hiebsch RR, Raub TJ, Wattenberg BW et al. J Biol Chem, 1991, 266:20323~20337
4 Kanakaraj P, Raj S, Khan SA et al. M Biochemistry, 1991, 30:1761~1767
5 Ostendorf T, KunterU, et al. The effects of platelet-derived growth factor inexperimental glomerulonephritis are independent of the transforming growthfactor-beta system. J Am Soc Nephrol, 2002, 13(3), 658~667
6 Ostendorf Tammo, van Roeyen, Claudia RC, et al. A fully human monoclonalantibody(CR002) identifies PDGF-D as a novel mediator of mesangioprolerative glomerulonephritis. Journal of the American Society of Nephrology, 2003, 14(9):2237~224
7 PawsonT, ScottJD. Signaling throughs caffold, anchoring, andadaptor proteins. Science, 1997, 278:2075~2080
8 Cartel NJ, Liu J. PDGF-BB-mediated activation of p42(MAPK) is independent of PDGF beta-receptor tyrosine phosphorylation. Am J Physiol LungCell Mol Physiol, 2001,281(4):L786~798
9 Jacob A, Molkentin JD, et al. Insulin inhibits PDGF-directed VSMC migration via NO/cGMP increase of MKP-1 and its inactivation of MAPKs.Am JPhysiol Cell Physiol, 2002, 283(3):4~13
10 Houdhury GG. Akt serine threonine kinase regulates platelet-derived growthfactor-induced DNA synthesis in glomerular mesangial cells: regulation ofAND p27(kip1) gene expression. J Biol Chem, 2001, 276(38), 35636~35643
11 Yu Y, Sweeney M, Zhang S, et al. PDGF stimulates pulmonary vascularsmooth muscle cell proliferation by upregulating TRPC6 expression.Am JPhysiol Cell Physiol, 2003, 284(2):316~330
12 Wang SN, Hirschberg R. Growth factor ultrafiltration in experimental diabetic nephropathy contributes to interstitial fibrosis. American Journal of Physiology Renal Electrolyte Physiology, 2000, 278(4):554~560
13 KingsleyK, RustWL, et al. PDGF-BB enhances expression of,and reducesadhesion to, laminin-5 in vascular smooth muscle cells. Biochem BiophysRes Commun, 2002, 294(5):1017~1022
14 Enter F, Ostendorf T, Van Roeyen C, et al. Expression of a novel PDGFisform, PDGF-C, in normal and diseased rat kidney. J Am Soc Nephrol. 2002, 13(4):910~917
15 Changsirikulchai S, Hudkins KL, et al. Platelet-derived growth factor-D expression in developing and mature humankidney. Kidney Int. 2002, 62(6):2043~2054
16 Gesualdo L, Pinzani M, Floriano JJ, et al. Lab Invest, 1991, 65:160~167
17 Terada Y, Yamada T, Nakashima O, et al. J Am Soc Nephrol, 1997, 8(5):817~819
18 Yoshimura A, Inui K, Suzuki T, et al. J Am Soc Nephrol, 1993, 4:692
19 Frank J, Engler-BlumG, RodemannHP, et al. Human renal tubular cellsas a cytokine source: PDGF-B, GM-CSF and IL-6 mRNA expressionin vitro. Experimental Nephrology, 1993, 1(1):26~35
20 Winson WT, Thomas RU, David LL et al. American Journal of Pathology, 1996, 148(4): 1169~1180
21 Gesualdo L Pinzani M, Floriano JJ et al. Lab Invest, 1991, 65:160~164
22 Fellstrom B, Klareskog L, Heldin CH et al. Kidney Int, 1989, 36:1099~1102
23 Taneda S, Hudkins KL, et al. Growth factor expression in a murine modelof cryoglobulinemia. Kidney Int, 2003, 63(2):576~590
24 Makino H, Sugiyama H, Kashihara N. Apoptosis and extracellular matrix-cell interactions in kidney disease. Kidney Int Suppl, 2000, 77:67~75
25 Paul-RV, Wackym-PS, Budisavljevic-MN. J Am Soc Nephrol, 1998, 9(1):26~32
26 Lida H,Seifert R, Alpers CE, et al. Proc Natl Acad Sci USA,1991, 88:6560~6564
27 Razzaque MS, Cheng M, Tagouchi T. J Comp Pathol, 1996, 114(2):175~182
28 Yoshimura A, Inui K, Suzuki T, et al. J Am Soc Nephrol, 1993, 4:692
29 Matsuda M, Shilata K, Makino H, et al. Am J Nephrol, 1997, 17(1):25~31
30 Abboud HE. Kidney Int, 1993, 43:252~257
31 Mackensen HS, Bohle A, Christensen J, et al. ClinNephrol, 1992, 37:70~77
32 Knecht A, Fine LG, Kleinmn KS, et al. Am J Physiol, 1991, 261:292~299
33 Lonnemann G, Miller GA, Koch KM. J Am Soc Nephrol, 1994, 755:756
34 Frank J,Engler-BlumG,RodemannHP,et al.Human renal tubular cellsas a cytokine source:PDGF-B,GM-CSF and IL-6 mRNA expression in vitro.Experimental Nephrology,1993,1(1):26~35
35 Tang WW, Ulich TR, Lacey DL, et al. Platelet derived growth factor-BB induces renal interstitial myofibroblast formation and tubulointerstitial fibrosis. AM J Pathology, 1996, 148(4):1169~1180
36 Ng YY, Huang TP, Wang Wc, et al. Tubular epithelial-Myofibroblast transdifferentiation in progressive tubulointerstitial fibrosis in 5/6 nephre-cotomized rats. Kidney Int, 1998, 54:864~876
37 Wang SN, Hirschberg R. Growth Factor ultrafiltration in experimental dia-betic nephropathy contributes to interstitial fibrosis. American Journal of Physiology Renal Electrolyte Physiology, 2002, 278(4):554~560
38 Floege, Jurgen, Eitner, et al. PDGF-D and renal disease:Yet Another One of Those Growth Factors, J Am Soc Nephrol, 2003, 14(10):2690~2691
39 Tang WW. PDGF-BB induces renal tubulointerstitial Myofibroblast formation and tubulointerstitial fibrosis. Am J Pathol, 1996, 148(4):1169~1180
40 Li X, Ponten A, Aase K, et al. PDGF-C is a new protease-activated lIgAnd for the PDGF alpha-receptor. Nat Cell Biol, 2002, 2:302~309
41 Taneda, Sekiko, Hudkins, et al. Obstructive Uropathy in Mice and humans: Potential role for PDGF-D in the Progression of Tubulointerstitial Injury. J Am Soc Nephrol, 2003, 14(10):2544~2555