吡格列酮对5/6肾切除大鼠PDGF-BB与MMP-9表达的影响
|
摘要
目的
观察吡格列酮(Pioglitzone, PGZ)对5/6肾切除大鼠血小板源性生长因子(platelet-derived growth factor, PDGF)与基质金属蛋白酶-9 ( matrix metalloproteinase-9, MMP-9)表达的影响,探讨其对肾小球硬化影响的可能机制。
方法
选取60只雄性SD大鼠,随机分为假手术组、模型组、PGZ组,每组20只,然后每组于8周和12周取10只处死进行检测指标。模型组和PGZ组大鼠按两步法行5/6肾切除建立肾小球硬化模型。假手术组仅分离肾周围脂肪组织暴露肾脏,缝合腹壁。末次手术后PGZ组给予PGZ(10mg/kg/d)灌胃,假手术组和模型组仅给予生理盐水。分别于术后8周、12周进行肾脏病理学分析,采取免疫组织化学和Western blotting检测肾组织PDGF-BB和MMP-9的表达。
结果
1.模型组系膜细胞明显增殖,系膜区细胞外基质(extracellular matrix, ECM)显著沉积,肾小球硬化指数(Glomerulosclerosis index, GSI)和肾小球ECM/肾小球面积(Glomerular area, GA)明显升高(p﹤0.05);PGZ组系膜细胞增殖以及系膜区ECM沉积明显减轻,GSI和ECM/GA明显降低(p﹤0.05)。
2.模型组PDGF-BB在肾小球表达增强,12周时表达最强,PGZ组在8周和12周时PDGF-BB表达较模型组减弱;模型组较假手术组MMP-9在肾小球表达减弱,12周时表达最弱,PGZ组8周和12周时较模型组MMP-9表达增强。
3. Western blotting结果显示,模型组PDGF-BB表达随时间逐渐升高,12周时升高最为明显,MMP-9表达随时间逐渐降低,12周时降低最为显著,而PGZ组于8周和12周时较模型组PDGF-BB表达显著降低,MMP-9表达显著升高(p﹤0.05)。
4. PDGF-BB与ECM/GA、GSI呈正相关(r=0.613、0.697, p<0.05)。MMP-9与ECM/GA、GSI呈负相关(r分别为-0.893、-0.764, p<0.05)。
结论
1. PGZ能显著抑制5/6肾切除大鼠系膜细胞的增殖,降低肾小球系膜区ECM的沉积,减轻肾小球毛细血管袢受压,最终延缓肾小球硬化的进展。
2. PGZ延缓肾小球硬化的机制可能与下调肾小球PDGF-BB的表达,进而抑制系膜细胞的过度增殖;上调MMP-9的表达,进而促进ECM降解有关。
Objective
To investigate the effect of pioglitzone on the expression of PDGF-BB and MMP-9 in the rat remnant kidney and further reveal the possible mechanisms of pioglitzone on glomerulosclerosis.
Methods
60 male Sprague-Dawley rats were randomly divided into 3 equal groups: sham group, model group and PGZ group. 10 rats were used to examine index in each group at 8 and 12 week. The rats in the latter two groups were subjected to 5/6 nephrectomy. Pioglitzone was orally administered for 12 weeks to PGZ group, but the rats in model group were only given 0.9% sodium chloride solution by gastrogavage as well as 12 weeks after operation. 0.9% sodium chloride solution was also fed for 12 weeks to rats that previously underwent sham operation. After the completion of administration period, the degree of renal injury was examined histopathologically. At 8 and 12 week, Immunohistochemichal staining and western blotting for PDGF-BB and MMP-9 were also performed.
Results
1. Rats that underwent 5/6 nephrectomy had more severe MC proliferation and ECM accumulation, greater GSI and ECM/GA than sham operated rats; The PGZ ameliorated these effects.
2. Immunohistochemistry showed that compared with sham operated group the expression of PDGF-BB in glomeruli increased, PGZ group decreased compared with model group; compared to sham operated group the reduction of MMP-9 was detected in glomeruli of model group, PGZ group increased compared to model group.
3. Glomeruli in 5/6 nephrectomized rats expressed higher levels of PDGF-BB and lower MMP-9 compared with sham group rats. PGZ group rats have lower levels of PDGF-BB and higher levels of MMP-9.
4. PDGF-BB was positively correlated with ECM/GA and GSI (r =0.613, 0.697, p<0.05); MMP-9 and ECM/GA, GSI was a negative correlation ( r = -0.893, -0.764, p<0.05).
Conclusions
1. PGZ significantly inhibited MC proliferation of 5/6 nephrectomized rats, reduced glomerular mesangial ECM deposition, and thereby delay the progress of glomerulosclerosis, ultimately improving kidney function.
2. These effects might be, partly, related to down-regulation of PDGF-BB, and up-regulation of MMP-9 in the remnant kidney.
观察吡格列酮(Pioglitzone, PGZ)对5/6肾切除大鼠血小板源性生长因子(platelet-derived growth factor, PDGF)与基质金属蛋白酶-9 ( matrix metalloproteinase-9, MMP-9)表达的影响,探讨其对肾小球硬化影响的可能机制。
方法
选取60只雄性SD大鼠,随机分为假手术组、模型组、PGZ组,每组20只,然后每组于8周和12周取10只处死进行检测指标。模型组和PGZ组大鼠按两步法行5/6肾切除建立肾小球硬化模型。假手术组仅分离肾周围脂肪组织暴露肾脏,缝合腹壁。末次手术后PGZ组给予PGZ(10mg/kg/d)灌胃,假手术组和模型组仅给予生理盐水。分别于术后8周、12周进行肾脏病理学分析,采取免疫组织化学和Western blotting检测肾组织PDGF-BB和MMP-9的表达。
结果
1.模型组系膜细胞明显增殖,系膜区细胞外基质(extracellular matrix, ECM)显著沉积,肾小球硬化指数(Glomerulosclerosis index, GSI)和肾小球ECM/肾小球面积(Glomerular area, GA)明显升高(p﹤0.05);PGZ组系膜细胞增殖以及系膜区ECM沉积明显减轻,GSI和ECM/GA明显降低(p﹤0.05)。
2.模型组PDGF-BB在肾小球表达增强,12周时表达最强,PGZ组在8周和12周时PDGF-BB表达较模型组减弱;模型组较假手术组MMP-9在肾小球表达减弱,12周时表达最弱,PGZ组8周和12周时较模型组MMP-9表达增强。
3. Western blotting结果显示,模型组PDGF-BB表达随时间逐渐升高,12周时升高最为明显,MMP-9表达随时间逐渐降低,12周时降低最为显著,而PGZ组于8周和12周时较模型组PDGF-BB表达显著降低,MMP-9表达显著升高(p﹤0.05)。
4. PDGF-BB与ECM/GA、GSI呈正相关(r=0.613、0.697, p<0.05)。MMP-9与ECM/GA、GSI呈负相关(r分别为-0.893、-0.764, p<0.05)。
结论
1. PGZ能显著抑制5/6肾切除大鼠系膜细胞的增殖,降低肾小球系膜区ECM的沉积,减轻肾小球毛细血管袢受压,最终延缓肾小球硬化的进展。
2. PGZ延缓肾小球硬化的机制可能与下调肾小球PDGF-BB的表达,进而抑制系膜细胞的过度增殖;上调MMP-9的表达,进而促进ECM降解有关。
Objective
To investigate the effect of pioglitzone on the expression of PDGF-BB and MMP-9 in the rat remnant kidney and further reveal the possible mechanisms of pioglitzone on glomerulosclerosis.
Methods
60 male Sprague-Dawley rats were randomly divided into 3 equal groups: sham group, model group and PGZ group. 10 rats were used to examine index in each group at 8 and 12 week. The rats in the latter two groups were subjected to 5/6 nephrectomy. Pioglitzone was orally administered for 12 weeks to PGZ group, but the rats in model group were only given 0.9% sodium chloride solution by gastrogavage as well as 12 weeks after operation. 0.9% sodium chloride solution was also fed for 12 weeks to rats that previously underwent sham operation. After the completion of administration period, the degree of renal injury was examined histopathologically. At 8 and 12 week, Immunohistochemichal staining and western blotting for PDGF-BB and MMP-9 were also performed.
Results
1. Rats that underwent 5/6 nephrectomy had more severe MC proliferation and ECM accumulation, greater GSI and ECM/GA than sham operated rats; The PGZ ameliorated these effects.
2. Immunohistochemistry showed that compared with sham operated group the expression of PDGF-BB in glomeruli increased, PGZ group decreased compared with model group; compared to sham operated group the reduction of MMP-9 was detected in glomeruli of model group, PGZ group increased compared to model group.
3. Glomeruli in 5/6 nephrectomized rats expressed higher levels of PDGF-BB and lower MMP-9 compared with sham group rats. PGZ group rats have lower levels of PDGF-BB and higher levels of MMP-9.
4. PDGF-BB was positively correlated with ECM/GA and GSI (r =0.613, 0.697, p<0.05); MMP-9 and ECM/GA, GSI was a negative correlation ( r = -0.893, -0.764, p<0.05).
Conclusions
1. PGZ significantly inhibited MC proliferation of 5/6 nephrectomized rats, reduced glomerular mesangial ECM deposition, and thereby delay the progress of glomerulosclerosis, ultimately improving kidney function.
2. These effects might be, partly, related to down-regulation of PDGF-BB, and up-regulation of MMP-9 in the remnant kidney.
引文
1 Kamanna VS, Bassa BV, Ganji SH, et al. Bioactive lysophospholipids and mesangial cell intracellular signaling pathways: role in the pathobiology of kidney disease. Histol Histopathol, 2005, 20(2):603-613.
2 Shimoda HK, Yamamoto M, Shide K, et al. Chronic thrombopoietin overexpression induces mesangioproliferative glomerulopathy in mice. Am J Hematol, 2007, 82(9):802-806.
3 Ko GJ, Kang YS, Han SY, et al. Pioglitazone attenuates diabetic nephropathy through an anti-inflammatory mechanism in type 2 diabetic rats. Nephrol Dial Transplant, 2008, 23(9):2750-2760.
4 Wan Z, Shi W, Shao B, et al. Peroxisome proliferator-activated receptorγagonist pioglitazone inhibitsβ-catenin-mediated glioma cell growth and invasion. Mol Cell Biochem, 2011, 349(1-2):1-10.
5邹荣,徐钢,刘晓城,等.曲格列酮影响大鼠系膜细胞增殖和凋亡的实验研究.华中科技大学学报(医学版), 2008, 37(5):681-683.
6 Isshiki K, Haneda M, Koya D, et al. Thiazolidinedione compounds ameliorate glomerular dysfunction independent of their insulin-sensitizing action in diabetic rats. Diabetes, 2000, 49(6):1022-1032.
7 Kim HJ, Vaziri ND, Norris K, et al. High-calorie diet with moderate protein restriction prevents cachexia and ameliorates oxidative stress, inflammation and proteinuria in experimental chronic kidney disease. Clin Exp Nephrol, 2010, 14(6):536-547.
8 Long Q, Li HM, Zhang LY, et al. Effects of low protein diet withα-ketoacids supplement on metabolism and residua kidney fibrosis in 5/6 nephrectomized rats. Shanghai Med J, 2009, 32(3):240-245.
9龙若庭,何泽云.怡肾汤对5/ 6肾切除大鼠残肾组织形态与Col-Ⅳ及MMP-2的干预作用.中国中西医结合肾病杂志, 2005, 7(6):324-327.
10宋锦叶,李深,孟立强,等.黄芪当归合剂对5/6肾切除大鼠肾组织损伤的治疗作用.北京大学学报(医学版), 2009, 41(2):196-202.
11 Dong FQ, Li H, Cai WM, et al. Effects of pioglitazone on expressions of matrix metalloproteinases 2 and 9 in kidneys of diabetic rats. Chinese Medical Journal, 2004, 117(7): 1040-1044.
12 Zafiriou S, Stanners SR, Saad S, et al. Pioglitazone inhibits cell growth and reduces matrix production in human kidney fibroblasts. J Am Soc Nephrol, 2005, 16(3):638-645.
13 Whiteside C, Wang H, Xia L, et al. Rosiglitazone prevents high glucose-induced vascular endothelial growth factor and collagen IV expression in cultured mesangialcells. Exp Diabetes Res, 2009, 2009:910783.
14 Senet P, Vicaut E, Beneton N, et al. Topical Treatment of Hypertensive Leg Ulcers With Platelet-Derived Growth Factor-BB: A Randomized Controlled Trial. Arch Dermatol, 2011, [Epub ahead of print].
15 Suzuki S, Dobashi Y, Hatakeyama Y, et al. Clinicopathological significance of platelet-derived growth factor (PDGF)-B and vascular endothelial growth factor-A expression, PDGF receptor-βphosphorylation, and microvessel density in gastric cancer. BMC Cancer, 2010, 10:659.
16 Lee HS, Song CY. Differential role of mesangial cells and podocytes in TGF-beta-induced mesangial matrix synthesis in chronic glomerular disease. Histol Histopathol, 2009, 24(7): 901-908.
17 Mima A, Abe H, Nagai K, et al. Activation of Src Mediates PDGF-Induced Smad1 Phosphorylation and Contributes to the Progression of Glomerulosclerosis in Glomerulonephritis. PLoS One, 2011, 6(3):e17929.
18 Hornigold N, Craven RA, Keen JN, et al. Upregulation of Hic-5 in glomerulosclerosis and its regulation of mesangial cell apoptosis. Kidney Int, 2010, 77(4): 329-338.
19 van Roeyen CR, Ostendorf T, Denecke B, et al. Biological responses to PDGF-BB versus PDGF-DD in human mesangial cells. Kidney Int, 2006, 69(8): 1393-1402.
20姜小宇,袁伟杰,孙莉静,等.金雀异黄素对血小板源性生长因子诱导大鼠肾小球系膜细胞增殖及细胞外基质的影响.中华肾脏病杂志, 2006, 22(12):777-778.
21吴伟玲,张爱青,殷勤,等. ERK通路抑制剂对PDGF-BB诱导的大鼠系膜细胞细胞外基质合成的影响.南京医科大学学报(自然科学版), 2007, 27(10):1126-1129.
22 Maeda A, Horikoshi S, Gohda T, et al. Pioglitazone attenuates TGF-beta(1)-induction of fibronectin synthesis and its splicing variant in human mesangial cells via activation of peroxisome proliferator-activated receptor (PPAR)gamma. Cell Biol Int, 2005, 29(6):422-428.
23 Okada T, Wada J, Hida K, et al. Thiazolidinediones ameliorate diabetic nephropathy via cell cycle-dependent mechanisms. Diabetes, 2006, 55(6):1666-1677.
24 Onozaki A, Midorikawa S, Sanada H, et al. Rapid change of glucose concentration promotes mesangial cell proliferation via VEGF: inhibitory effects of thiazolidinedione. Biochem Biophys Res Commun, 2004, 317(1):24-29.
25 Liu S, Li Y, Zhao H, et al. Increase in extracellular cross-linking by tissue transglutaminase and reduction in expression of MMP-9 contribute differentially to focal segmental glomerulosclerosis in rats. Mol Cell Biochem, 2006, 284(1-2):9-17.
26 Qin YH, Lei FY, Hu P, et al. Effect of all-trans retinoic acid on renal expressions of matrix metalloproteinase-2, matrix metalloproteinase-9 and tissue inhibitor of metallo-proteinase-1 in rats with glomerulosclerosis. Pediatr Nephrol, 2009, 24(8):1477-1486.
27 Liu WH, Tang NN, Zhang QD. Could mycophenolate mofetil combined with benazapril delay tubulointerstitial fibrosis in 5/6 nephrectomized rats? Chin Med J, 2009, 122(2): 199-204.
28 Iekushi K, Taniyama Y, Azuma J, et al. Hepatocyte growth factor attenuates renal fibrosis through TGF-β1 suppression by apoptosis of myofibroblasts. J Hypertens, 2010, 28(12):2454-2461.
29 Zou R, Xu G, Liu XC, et al. PPARgamma agonists inhibit TGF-beta-PKA signaling in glomerulosclerosis. Acta Pharmacol Sin, 2010, 31(1):43-50.
30 Zafiriou S, Stanners SR, Saad S, et al. Pioglitazone inhibits cell growth and reduces matrix production in human kidney fibroblasts. J Am Soc Nephrol, 2005, 16(3):638-645.
1 Nakagawa T, Izumino K, Ishii Y, et al. Roles of PDGF receptor-beta in the structure and function of postnatal kidney glomerulus. Nephrol Dial Transplant, 2011, 26(2):458-468.
2 Eitner F, Bücher E, van Roeyen C, et al. PDGF-C is a proinflammatory cytokine that mediates renal interstitial fibrosis. J Am Soc Nephrol, 2008, 19(2):281-289.
3 Floege J, van Roeyen C, Boor P, et al. The role of PDGF-D in mesangioproliferative glomerulonephritis. Contrib Nephrol, 2007, 157:153-158.
4 Zou R, Xu G, Liu XC, et al. PPARgamma agonists inhibit TGF-beta-PKA signaling in glomerulosclerosis. Acta Pharmacol Sin, 2010, 31(1):43-50.
5冯大莺.狼疮肾炎肾组织细胞表型转化a-SMA的表达与临床相关性的研究:[硕士学位论文].昆明:昆明医学院第一临床学院, 2008.
6 Simonson MS. Phenotypic transitions and fibrosis in diabetic nephropathy. Kidney Int, 2007, 71(9):846-854.
7颜润.血小板源性生长因子-B在间质纤维化模型大鼠肾组织中的表达及意义.贵州医药, 2009, 33(6):486-489.
8 Sommer M, Gerth J, Stein G, et al. Transdifferentiation of endothelial and renal tubular epithelial cells into myofibroblast-like cells under in vitro conditions:a morphological analysis. Cells Tissues Organs, 2005, 180(4): 204-214.
9 Velasco-Loyden G, Pérez-Carreón JI, Agüero JF, et al. Prevention of in vitro hepatic stellate cells activation by the adenosine derivative compound IFC305. Biochem Pharmacol, 2010, 80(11):1690-1699.
10张莹,王荣,王群,等.益肾活血汤通过p38MAPK信号途径调控系膜细胞纤连蛋白及Ⅳ型胶原的研究.山东大学学报(医学版), 2009, 47(9):66-69.
11 Hardy J, Hambly B, Ko H, et al. Stimulation of mesangial cells by angiotensin II and lipopolysaccharide increases expression of interleukin-18, but not IL-18 receptor. Nephron Exp Nephrol, 2010, 116(4):e63-71.
12 Kruglov EA, Nathanson RA, Nguyen T, et al. Secretion of MCP-1/CCL2 by bile duct epithelia induces myofibroblastic transdifferentiation of portal fibroblasts. Am J Physiol Gastrointest Liver Physiol, 2006, 290(4):G765-771.
13 Kawano H, Kim S, OhtaK, et al. Differential contribution of three mitogen-activated protein kinases to PDGF-BB induced mesangial cell proliferation and gene expression. J Am Soc Nephrol, 2003, 14(3):584-592.
14洪寅峰,张志刚,高山.狼疮性肾炎中u-PA和PAI-1的表达及其意义.上海医学, 2001, 24(3):169-172.
15吴伟玲,张爱青,殷勤,等. ERK通路抑制剂对PDGF-BB诱导的大鼠系膜细胞细胞外基质合成的影响.南京医科大学学报(自然科学版), 2007, 27(10):1126-1129.
16周巧玲,杨敬华,彭卫生,等.金属基质蛋白酶9及其组织抑制物1在肾组织中的表达和调控.肾脏病与透析肾移植杂志, 2007, 16(2):134-140.
17 Liu WH, Tang NN, Zhang QD. Could mycophenolate mofetil combined with benazapril delay tubulointerstitial fibrosis in 5/6 nephrectomized rats? Chin Med J, 2009, 122(2): 199-204.
18 van Roeyen CR, T Ostendorf, B Denecke, et al. Biological responses to PDGF-BB versus PDGF-DD in human mesangial cells. Kidney Int, 2006, 69(8):1393-1402.
19姜小宇,袁伟杰,孙莉静,等.金雀异黄素对血小板源性生长因子诱导大鼠肾小球系膜细胞增殖及细胞外基质的影响.中华肾脏病杂志, 2006, 22(12):777-778.
20邹丽萍,蒋涛,车祺,等.醛糖还原酶抑制剂影响PDGF-BB促系膜细胞增殖作用的机制研究.复旦学报(医学版), 2007, 34(4):557-562.
21 Ostendorf T, Rong S, Boor P, et al. Antagonism of PDGF-D by human antibody CR002 prevents renal scarring in experimental glomerulonephritis. J Am Soc Nephrol, 2006, 17(4):1054-62.
22 Rong ZH, Wang C, Hao J, et al. Expression and clinical implication of platelet-derived growth factor-D and platelet-derived growth factor-beta in childhood IgA nephropathy. Chin Crit Care Med, 2008, 20(5):275-278.
23戎赞华,齐钊,史永红,等. PDGF-D在儿童IgA肾病中的表达增加.基础医学与临床, 2008, 28(12):1313-1314.
24 Boor P, Eitner F, Cohen CD, et al. Patients with IgA nephropathy exhibit high systemic PDGF-DD levels. Nephrol Dial Transplant, 2009, 24(9):2755-2762.
25 Imasawa T, Kitamura H, Ohkawa R. Unbalanced expression of sphingosine 1-phosphate receptors in diabetic nephropathy. Experimental and Toxicologic Pathology, 2010, 62(1):53 -60.
26 Wang QY, Guan QH, Chen FQ. The changes of platelet-derived growth factor-BB (PDGF-BB) in T2DM and its clinical significance for early diagnosis of diabetic nephropathy. Diabetes Res Clin Pract, 2009, 85(2):166-170.
27 Taneda S, Hudkins KL, Cui Y, et al. Growth factor expression in a murine model of cryoglobulinemia. Kidney Int, 2003, 63(2):576-590.
28 Lassila M, Jandeleit-Dahm K, SeahK K, et al. Imatinib attenuates diabetic nephropathy in apolipoprotein E-knockout mice. J Am Soc Nephrol, 2005, 16(2):363-373.
29韩子明,樊爱英,梁秀玲,等.洛伐他汀降脂治疗对肾病大鼠血小板源生长因子表达的影响.中国现代医学杂志, 2004, 14(13):34-40.
2 Shimoda HK, Yamamoto M, Shide K, et al. Chronic thrombopoietin overexpression induces mesangioproliferative glomerulopathy in mice. Am J Hematol, 2007, 82(9):802-806.
3 Ko GJ, Kang YS, Han SY, et al. Pioglitazone attenuates diabetic nephropathy through an anti-inflammatory mechanism in type 2 diabetic rats. Nephrol Dial Transplant, 2008, 23(9):2750-2760.
4 Wan Z, Shi W, Shao B, et al. Peroxisome proliferator-activated receptorγagonist pioglitazone inhibitsβ-catenin-mediated glioma cell growth and invasion. Mol Cell Biochem, 2011, 349(1-2):1-10.
5邹荣,徐钢,刘晓城,等.曲格列酮影响大鼠系膜细胞增殖和凋亡的实验研究.华中科技大学学报(医学版), 2008, 37(5):681-683.
6 Isshiki K, Haneda M, Koya D, et al. Thiazolidinedione compounds ameliorate glomerular dysfunction independent of their insulin-sensitizing action in diabetic rats. Diabetes, 2000, 49(6):1022-1032.
7 Kim HJ, Vaziri ND, Norris K, et al. High-calorie diet with moderate protein restriction prevents cachexia and ameliorates oxidative stress, inflammation and proteinuria in experimental chronic kidney disease. Clin Exp Nephrol, 2010, 14(6):536-547.
8 Long Q, Li HM, Zhang LY, et al. Effects of low protein diet withα-ketoacids supplement on metabolism and residua kidney fibrosis in 5/6 nephrectomized rats. Shanghai Med J, 2009, 32(3):240-245.
9龙若庭,何泽云.怡肾汤对5/ 6肾切除大鼠残肾组织形态与Col-Ⅳ及MMP-2的干预作用.中国中西医结合肾病杂志, 2005, 7(6):324-327.
10宋锦叶,李深,孟立强,等.黄芪当归合剂对5/6肾切除大鼠肾组织损伤的治疗作用.北京大学学报(医学版), 2009, 41(2):196-202.
11 Dong FQ, Li H, Cai WM, et al. Effects of pioglitazone on expressions of matrix metalloproteinases 2 and 9 in kidneys of diabetic rats. Chinese Medical Journal, 2004, 117(7): 1040-1044.
12 Zafiriou S, Stanners SR, Saad S, et al. Pioglitazone inhibits cell growth and reduces matrix production in human kidney fibroblasts. J Am Soc Nephrol, 2005, 16(3):638-645.
13 Whiteside C, Wang H, Xia L, et al. Rosiglitazone prevents high glucose-induced vascular endothelial growth factor and collagen IV expression in cultured mesangialcells. Exp Diabetes Res, 2009, 2009:910783.
14 Senet P, Vicaut E, Beneton N, et al. Topical Treatment of Hypertensive Leg Ulcers With Platelet-Derived Growth Factor-BB: A Randomized Controlled Trial. Arch Dermatol, 2011, [Epub ahead of print].
15 Suzuki S, Dobashi Y, Hatakeyama Y, et al. Clinicopathological significance of platelet-derived growth factor (PDGF)-B and vascular endothelial growth factor-A expression, PDGF receptor-βphosphorylation, and microvessel density in gastric cancer. BMC Cancer, 2010, 10:659.
16 Lee HS, Song CY. Differential role of mesangial cells and podocytes in TGF-beta-induced mesangial matrix synthesis in chronic glomerular disease. Histol Histopathol, 2009, 24(7): 901-908.
17 Mima A, Abe H, Nagai K, et al. Activation of Src Mediates PDGF-Induced Smad1 Phosphorylation and Contributes to the Progression of Glomerulosclerosis in Glomerulonephritis. PLoS One, 2011, 6(3):e17929.
18 Hornigold N, Craven RA, Keen JN, et al. Upregulation of Hic-5 in glomerulosclerosis and its regulation of mesangial cell apoptosis. Kidney Int, 2010, 77(4): 329-338.
19 van Roeyen CR, Ostendorf T, Denecke B, et al. Biological responses to PDGF-BB versus PDGF-DD in human mesangial cells. Kidney Int, 2006, 69(8): 1393-1402.
20姜小宇,袁伟杰,孙莉静,等.金雀异黄素对血小板源性生长因子诱导大鼠肾小球系膜细胞增殖及细胞外基质的影响.中华肾脏病杂志, 2006, 22(12):777-778.
21吴伟玲,张爱青,殷勤,等. ERK通路抑制剂对PDGF-BB诱导的大鼠系膜细胞细胞外基质合成的影响.南京医科大学学报(自然科学版), 2007, 27(10):1126-1129.
22 Maeda A, Horikoshi S, Gohda T, et al. Pioglitazone attenuates TGF-beta(1)-induction of fibronectin synthesis and its splicing variant in human mesangial cells via activation of peroxisome proliferator-activated receptor (PPAR)gamma. Cell Biol Int, 2005, 29(6):422-428.
23 Okada T, Wada J, Hida K, et al. Thiazolidinediones ameliorate diabetic nephropathy via cell cycle-dependent mechanisms. Diabetes, 2006, 55(6):1666-1677.
24 Onozaki A, Midorikawa S, Sanada H, et al. Rapid change of glucose concentration promotes mesangial cell proliferation via VEGF: inhibitory effects of thiazolidinedione. Biochem Biophys Res Commun, 2004, 317(1):24-29.
25 Liu S, Li Y, Zhao H, et al. Increase in extracellular cross-linking by tissue transglutaminase and reduction in expression of MMP-9 contribute differentially to focal segmental glomerulosclerosis in rats. Mol Cell Biochem, 2006, 284(1-2):9-17.
26 Qin YH, Lei FY, Hu P, et al. Effect of all-trans retinoic acid on renal expressions of matrix metalloproteinase-2, matrix metalloproteinase-9 and tissue inhibitor of metallo-proteinase-1 in rats with glomerulosclerosis. Pediatr Nephrol, 2009, 24(8):1477-1486.
27 Liu WH, Tang NN, Zhang QD. Could mycophenolate mofetil combined with benazapril delay tubulointerstitial fibrosis in 5/6 nephrectomized rats? Chin Med J, 2009, 122(2): 199-204.
28 Iekushi K, Taniyama Y, Azuma J, et al. Hepatocyte growth factor attenuates renal fibrosis through TGF-β1 suppression by apoptosis of myofibroblasts. J Hypertens, 2010, 28(12):2454-2461.
29 Zou R, Xu G, Liu XC, et al. PPARgamma agonists inhibit TGF-beta-PKA signaling in glomerulosclerosis. Acta Pharmacol Sin, 2010, 31(1):43-50.
30 Zafiriou S, Stanners SR, Saad S, et al. Pioglitazone inhibits cell growth and reduces matrix production in human kidney fibroblasts. J Am Soc Nephrol, 2005, 16(3):638-645.
1 Nakagawa T, Izumino K, Ishii Y, et al. Roles of PDGF receptor-beta in the structure and function of postnatal kidney glomerulus. Nephrol Dial Transplant, 2011, 26(2):458-468.
2 Eitner F, Bücher E, van Roeyen C, et al. PDGF-C is a proinflammatory cytokine that mediates renal interstitial fibrosis. J Am Soc Nephrol, 2008, 19(2):281-289.
3 Floege J, van Roeyen C, Boor P, et al. The role of PDGF-D in mesangioproliferative glomerulonephritis. Contrib Nephrol, 2007, 157:153-158.
4 Zou R, Xu G, Liu XC, et al. PPARgamma agonists inhibit TGF-beta-PKA signaling in glomerulosclerosis. Acta Pharmacol Sin, 2010, 31(1):43-50.
5冯大莺.狼疮肾炎肾组织细胞表型转化a-SMA的表达与临床相关性的研究:[硕士学位论文].昆明:昆明医学院第一临床学院, 2008.
6 Simonson MS. Phenotypic transitions and fibrosis in diabetic nephropathy. Kidney Int, 2007, 71(9):846-854.
7颜润.血小板源性生长因子-B在间质纤维化模型大鼠肾组织中的表达及意义.贵州医药, 2009, 33(6):486-489.
8 Sommer M, Gerth J, Stein G, et al. Transdifferentiation of endothelial and renal tubular epithelial cells into myofibroblast-like cells under in vitro conditions:a morphological analysis. Cells Tissues Organs, 2005, 180(4): 204-214.
9 Velasco-Loyden G, Pérez-Carreón JI, Agüero JF, et al. Prevention of in vitro hepatic stellate cells activation by the adenosine derivative compound IFC305. Biochem Pharmacol, 2010, 80(11):1690-1699.
10张莹,王荣,王群,等.益肾活血汤通过p38MAPK信号途径调控系膜细胞纤连蛋白及Ⅳ型胶原的研究.山东大学学报(医学版), 2009, 47(9):66-69.
11 Hardy J, Hambly B, Ko H, et al. Stimulation of mesangial cells by angiotensin II and lipopolysaccharide increases expression of interleukin-18, but not IL-18 receptor. Nephron Exp Nephrol, 2010, 116(4):e63-71.
12 Kruglov EA, Nathanson RA, Nguyen T, et al. Secretion of MCP-1/CCL2 by bile duct epithelia induces myofibroblastic transdifferentiation of portal fibroblasts. Am J Physiol Gastrointest Liver Physiol, 2006, 290(4):G765-771.
13 Kawano H, Kim S, OhtaK, et al. Differential contribution of three mitogen-activated protein kinases to PDGF-BB induced mesangial cell proliferation and gene expression. J Am Soc Nephrol, 2003, 14(3):584-592.
14洪寅峰,张志刚,高山.狼疮性肾炎中u-PA和PAI-1的表达及其意义.上海医学, 2001, 24(3):169-172.
15吴伟玲,张爱青,殷勤,等. ERK通路抑制剂对PDGF-BB诱导的大鼠系膜细胞细胞外基质合成的影响.南京医科大学学报(自然科学版), 2007, 27(10):1126-1129.
16周巧玲,杨敬华,彭卫生,等.金属基质蛋白酶9及其组织抑制物1在肾组织中的表达和调控.肾脏病与透析肾移植杂志, 2007, 16(2):134-140.
17 Liu WH, Tang NN, Zhang QD. Could mycophenolate mofetil combined with benazapril delay tubulointerstitial fibrosis in 5/6 nephrectomized rats? Chin Med J, 2009, 122(2): 199-204.
18 van Roeyen CR, T Ostendorf, B Denecke, et al. Biological responses to PDGF-BB versus PDGF-DD in human mesangial cells. Kidney Int, 2006, 69(8):1393-1402.
19姜小宇,袁伟杰,孙莉静,等.金雀异黄素对血小板源性生长因子诱导大鼠肾小球系膜细胞增殖及细胞外基质的影响.中华肾脏病杂志, 2006, 22(12):777-778.
20邹丽萍,蒋涛,车祺,等.醛糖还原酶抑制剂影响PDGF-BB促系膜细胞增殖作用的机制研究.复旦学报(医学版), 2007, 34(4):557-562.
21 Ostendorf T, Rong S, Boor P, et al. Antagonism of PDGF-D by human antibody CR002 prevents renal scarring in experimental glomerulonephritis. J Am Soc Nephrol, 2006, 17(4):1054-62.
22 Rong ZH, Wang C, Hao J, et al. Expression and clinical implication of platelet-derived growth factor-D and platelet-derived growth factor-beta in childhood IgA nephropathy. Chin Crit Care Med, 2008, 20(5):275-278.
23戎赞华,齐钊,史永红,等. PDGF-D在儿童IgA肾病中的表达增加.基础医学与临床, 2008, 28(12):1313-1314.
24 Boor P, Eitner F, Cohen CD, et al. Patients with IgA nephropathy exhibit high systemic PDGF-DD levels. Nephrol Dial Transplant, 2009, 24(9):2755-2762.
25 Imasawa T, Kitamura H, Ohkawa R. Unbalanced expression of sphingosine 1-phosphate receptors in diabetic nephropathy. Experimental and Toxicologic Pathology, 2010, 62(1):53 -60.
26 Wang QY, Guan QH, Chen FQ. The changes of platelet-derived growth factor-BB (PDGF-BB) in T2DM and its clinical significance for early diagnosis of diabetic nephropathy. Diabetes Res Clin Pract, 2009, 85(2):166-170.
27 Taneda S, Hudkins KL, Cui Y, et al. Growth factor expression in a murine model of cryoglobulinemia. Kidney Int, 2003, 63(2):576-590.
28 Lassila M, Jandeleit-Dahm K, SeahK K, et al. Imatinib attenuates diabetic nephropathy in apolipoprotein E-knockout mice. J Am Soc Nephrol, 2005, 16(2):363-373.
29韩子明,樊爱英,梁秀玲,等.洛伐他汀降脂治疗对肾病大鼠血小板源生长因子表达的影响.中国现代医学杂志, 2004, 14(13):34-40.