IgA肾病肾小管间质损害与临床指标的相关分析
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摘要
目的:IgA肾病自1968年首先报导以来,已被认为是世界上最常见的原发性肾小球疾病。初期,人们认为该病预后良好。近年研究发现,在确诊后20~25年内患者呈进行性发展,20%~30%不可逆转地进展为终末期肾病(end-stage renal disease,ESRD)。肾组织学分级系统有助于比较IgAN肾活检标本和预测自然病程。本文首先回顾性研究既往6年678例IgAN肾活检标本,分析肾脏组织学分级及肾小管间质损害(TIL)与临床、实验室资料之间的关系。其次,研究不同级别的TIL肾活检组织中结缔组织生长因子(CTGF),磷酸化P38有丝分裂原活化蛋白激酶(phosphorylaed-P38 mitogen activated protein kinase,P-P38MAPK)及转化生长因子(TGF-β1)的表达情况,并探讨它们在肾小管间质损害进程中的作用。并进一步前瞻性对照研究IgA肾病患者Th细胞亚群紊乱与临床表现、TIL之间的关系,及其在发病机制中的作用。最后,探讨了黄芪注射液对IgAN患者肾小管功能的影响,并分析肾小管功能(尿视黄醇结合蛋白Urinary retinol binding protein,RBP及尿N-乙酰-β-D氨基葡萄糖苷酶N-acetyl-β-D- glucosaminidase,UNAG)与IgA肾病患者间质病理损害程度之间的关系,为进一步研究IgA肾病的发病机制及防治措施提供理论依据。
     方法:
     1.678例IgA肾病肾小管间质损害与临床指标的相关分析收集经临床及肾活检证实的678例原发性IgA肾病患者的病理与临床资料。光镜下观察方法:参考Lee分级标准和Haas分型标准,并根据小管间质损害病理学特点,对肾小管间质病变严重程度采用半定量积分评价。比较不同类型肾小管间质病变IgA肾病患者之间临床表现、实验室检查及肾活检病理的特点。
     2.IgA肾病患者CTGF、P38MAPK在TGF-β1致肾脏纤维化中的作用
     肾小管-间质病理指标参考Haas分型标准,将IgAN患者分为下列三组:1.轻度增生组(HaasⅠ、Ⅱ型)2.局灶增生组(HaasⅢ型)3.增生硬化组
Objectives: IgA nephropathy (IgAN) was first described in 1968 and is now recognized as the commonest primary glomerulopathy.The long-term outcome was initially thought to be benign but several series have reported highly variable prognosis with up to 20~30% of patients with IgAN developing end-stage renal disease (ESRD) within 20~25 years of diagnosis.The histologic grading system is useful to compare biopsy specimens and to predict the natural course of disease in IgA nephropathy (IgAN), although none of grading system is perfect. Firstly,The purpose of this retrospective study over a period of 6 years 678 renal biopsies was to investigate the relationship of the histologic grading, tubulointerstitial lesions(TIL) and clinical,laboratory data. secondly,To study the expression of connective tissue growth factor(CTGF), the phosphorylaed p38 Mitogen-Activated Protein Kinase (p-p38MAPK) Mediates TGF-β1–Induced Fibrogenesis in renal tissues of patients with IgA nephropathy. and theirs relationship with different grade tubulointerstital lession (TIL).Thirdly,To investigate the relationship of imbalance of T cell subpopulations and pathogenesis, clinical manifestation, as well as TIL of IgA nephropathy in prospective and controlled trial. Finally, To probe the effects of astragalus injection (AI) on renal tubular function in patients with IgAN and analyze the relationship of the renal tubular function (urinary retinol binding protein,RBP;N-acetyl-β-D-glucosaminidase,UNAG) and the severity of tubulointerstitial lesion. In order to further investigate the pathogenesis and preventional measure of IgA nephropathy.
     Methods:
     1. Study on the associations of the tubulointerstitial lesions with clinical indices in 678 cases of IgA nephropathy
     The clinical、laboratory and histopathological data in 678 patients with
引文
1 Berger J,Hinglais N.Les dép?ts intercapilaires d 'IgA-IgG.J Urol Néphrol,1968,74(9):694~695.
    2 Donadio JV, Grande JP. IgA nephropathy. N Engl J Med,2002,347 (10):738~748.
    3 Rai A,Nast C,Adler S.Henoch-Schonlein purpura nephritis. J Am Soc Nephrol,1999,10(12):2637~2644.
    4 Simon P,Ramee MP,Autuly V,et al. Epidemiology of primary glomerular diseases in a French region: variations according to period and age. Kidney Int,1994,46(4):1192~1198
    5 Wyat RJ, Julian BA, Baehler RW, et al. Epidemiology of IgA nephropathy in central and eastern Kentucky for the period 1975 through 1994.Central Kentucky Region of the Southeastern United States IgA Nephropathy DATABANK Project.J Am Soc Nephrol,1998,9(5):853~858.
    6 Levy M, Berger J.Worldwide perspective of IgA nephropathy.Am J Kidney Dis,1988,12(5):340~347.
    7 Li LS, Liu ZH.Epidemiologic data of renal diseases from a single unit in China: analysis based on 13,519 renal biopsies.Kidney Int,2004,66(3): 920~923.
    8 Cherpillod A, Moll S, Venetz JP, et al.IgA nephropathy: what you haveneed to know in 2005.Rev Med Suisse,2005,1(8):551~554,556.
    9 解放军肾脏病研究所学术委员会.IgA肾病诊断及治疗规范. 肾脏病与透析肾移植杂志,2004,13(3):253~255.
    10 D'Amico G. Natural history of idiopathic IgA nephropathy: role of clinical and histological prognostic factors.Am J Kidney Dis,2000,36(2):227~237.
    11 Syrjanen J, Mustonen J, Pasternack A. Hypertriglyceridaemia and hyperuricaemia are risk factors for progression of IgA nephropathy. Nephrol Dial Transplant,2000,15(1):34~42.
    12 D'Amico G,Imbasciati E, Barbiano Di Belgioioso G,et al.Idiopathic IgA mesangial nephropathy.Clinical and histological study of 374 patients. Medicine,1985,64(1):49~60.
    13 Kobayashi Y, Tateno S, Hiki Y, et al. IgA nephropathy: Prognostic significance of proteinuria and histological alterations.Nephron,1983,34 (3):146~153.
    14 Croker BP, Dawson DV,Sanfilippo F.IgA nephropathy. Correlation of clinical and histologic features.Lab Invest,1983,48(1):19~24.
    15 Levy M,Gonzales-Burchard G,Broyer M,et al.Berger's disease in children.Natural history and outcome.Medicine,1985,64(3):157~180.
    16 Bogenschutz O,Bohle A,Batz C,et al.IgA Nephritis:On the importance of morphological and clinical parameters in the long term prognosis of 239 patients.Am J Nephrol,1990,10(2):137~147.
    17 Alamartine E,Sabatier JC,Guerin C,et al.Prognostic factors in mesangial IgA glomerulonephritis: An extensive study with univariate and multivariate analysis.Am J Kid Dis,1991,18(1):12~19.
    18 邹 万 忠 . 肾 活 检 病 理 诊 断 标 准 指 导 意 见 . 中 华 肾 脏 病 杂志,2001,17(4):270~275.
    19 1999 World Health Organization-Internation Society of Hypertension Guidelines for the Management of Hypertension.Guideline Sub-committee. J Hypertens,1999,17:151~183.
    20 Pirani CL. Evaluation of kidney biopsy specimens. In: Tisher CC, BrennerBM, eds. Renal Pathology with Clinical and Functional Correlations.2nd edn.JB Lippincott Philadelphia,1994,85~115.
    21 Lee SM, Rao VM, Franklin WA, et al. IgA nephropathy: Morphologic predictors of progressive renal disease.Hum Pathol,1982,13(4):314~322.
    22 Haas M. IgA nephropathy histologically resembling focal-segmental glomerulosclerosis:A clinicopathologic study of 18 cases.Am J Kidney Dis,1996,28(3):365~371.
    23 Katafuchi R, Kiyoshi Y, Oh Y, et al. Glomerular score as a prognostic- cator in IgA nephropathy: its usefulness and limitation. Clin Nephro1, 1998,49(1):1~8.
    24 Haas M. Histologic subclassification of IgA nephropathy: A clinico- pathologic study of 244 cases.Am J Kidney Dis,1997,29(6):829~842.
    25 Lee SM.Prognostic indicators of progressive renal disease in IgA nephropathy: Emergence of a new histologic grading system.Am J Kidney Dis,1997,29(6):953~958.
    26 Radford MG Jr, Donadio JV Jr, Bergstralh EJ, et al. Predicting renal outcome in IgA nephropathy.J Am Soc Nephrol,1997,8(2):199~207.
    27 D′Amico G,Minetti L,Ponticelli C, et al. Prognostic indicators in idiopathic IgA mesangial nephropathy.Q J Med,1986,59(228):363~378.
    28 Myllym?ki J, Honkanen T, Syrj?nen J,et al. Uric acid correlates with the severity of histopathological parameters in IgA nephropathy.Nephrol Dial Transplant,2005,20(30): 89~95
    29 Noel LH, Droz D, Gascon M, et al. Primary IgA nephropathy: From the first described cases to the present.Semin Nephrol,1987,7(4):351~354.
    30 Norman JT, Clark IM, Garcia PL. Hypoxia Promotes fibrogenesis in human renal fibroblasts.Kidney Int,2000,58(6):2351~2366.
    31 Kang DH,Nakagawa T,Feng L,et al.Changes in renal micro-and macrovasculature induced by inhibition of nitric oxide synthesis in the remnant kidney model: New mechanism for progression of renal disease.J Am Soc Neprol,2001,12:816A.~817A..
    32 Takahikoa N, Duk-Heeb K, Ryujia R,et al.Tubulointerstitial disease: roleof ischemia and microvascular disease.Curr Opin Nephrol hypertens, 2003,12(3):233~241.
    33 Ryuji O,Hiroshi K.Peritubular capillary injury during progression of experimental glomerulonephritis in rats.J Am Neprol,2000,11(1):47~56.
    34 D'Amico. Emerging risk factors for the progression of renal disease: the clinical role of proteinuria. Am J Kidney Dis,1991,17(1):48~52.
    35 Sabadini E, Castiglione A, Coalasanti G, et al. Characterization of interstitial infiltrating cells in Berger's disease. Am J Kidney Dis,1988, 12(4):307~315.
    1 Badid C,Mounier N,Costa AM,et al.Role of myofibroblasts duringnormal tissue repair and excessive scaring:interest of their assessment in nephropathies.HistolHistopathol,2000,15(1):269~280.
    2 Wang Y,Li XM,Zou WZ,et al.Phenotypic changes of renal tubulointerstitial cells in human glomerulonephritis.Chin J Nephrol, 2000,16(1):7~10. 王玉,李晓玫,邹万忠.人类肾小球肾炎中肾小管及间质细胞表型转化的研究.中华肾脏病杂志,2000,16(1):7~10.
    3 Rastaldi MP,Ferrario F,Giardino L,et al. Epithelial-mesenchymal transition of tubular epithelial cells in human renal biopsies. Kidney International,2002,62(1):137~146.
    4 Bokemeyer D,Panek D,Kramer HJ,et al. In vivo identification of the mitogen-activated protein kinase cascade as a central pathogenic pathway in experimental mesangioproliferative glomerulonephritis. J Am Soc Nephrol,2002,13(6):1473~1480.
    5 Stambe C,Atkins RC,Tesch GH,et al. Blockade of p38alpha MAPK ameliorates acute inflammatory renal injury in rat anti-GBM glomerulonephritis.J AM Soc Nephrol,2003,14(2):338~351.
    6 Hass M.Histologic subclassification of IgA nephropathy:a clinicopathologic study of 244 cases.Am J Kidney Dis,1997,29(6):829~842.
    7 Zeisberg M,Kalluri R.The role of epithelial-to-mesenchymal transition in renal fibrosis.J Mol Med,2004,82(3):175~181.
    8 Zeiberg M,Struz F,Muller GA.Renal fibrosis: an update.Curr Opin Nephrol Hypertens,2001,10(3):315~320.
    9 Kalluri R,Neilson EG.Epithelial-mesenchymal transition and its implications for fibrosis.J Clin Invest,2003,112(12):1776~1784.
    10 Matsuda M,Shikata K,Makino H,et al.Glomerular expression of macrophage colony-stimulating factor and granulocyte-macrophage colony-stimulating factor in patients with various forms of glomerulonephritis. Lab Invest,1996,75(3):403~412.
    11 Utsunomiya Y,Kawamura T,Abe A,et al.Significance of mesangialexpression of alpha-smooth muscle actin in the progression of IgA nephropathy.Am J Kidney Dis,1999,34(5):902~910.
    12 Ng YY,Huang TP,Yang WC,et al.Tubular epithelial-myofibroblast transdifferentiation in progressive tubulointerstitial fibrosisin 5/6 nephrectomized rats.Kidney Int,1998,54(3):864~876.
    13 Omori S,Hida M,Ishikura K,et al.Expression of mitogen-activated protein kinase family in rat renal development.Kidney Int,2000,58(1):27~37.
    14 Bokemeyer D,Ostendorf T,Kunter U,et al.Differential activation of mitotogen-activated protein kinases in experimental mesangioproliferative glomerulonephritis.J Am Soc Nephrol,2000,11(2):232~240.
    15 Stambe C, Atkins RC, Hill PA, et al. Activation and cellular localization of the p38 and JNK MAPK pathways in rat crescentic glomerulonephritis. Kidney Int,2003,64(6):2121~2132.
    16 Dai C,Yang J W,Liu Y H. Transforming growth factor-β1 potentiates renal tubular epithelial cell death by a mechanism independent of Smad signaling.J Biol Chem,2003,278(14):12537~12545.
    17 McGinn S,Saad S,Poronnik P.High glucose-mediated effects on endothelial cell proliferation occur via p38 MAP kinase.Am J Physiol Endocrinol Metab. 2003,285(4):E708~717.
    18 Oka H,Chatani Y,Hoshino R,et al.Constitutive activation of mitogen- activated protein (MAP) kinases in human renal cell carcinoma.Cancer Res,1995,55(18):4182~4187.
    19 Stambe C,Atkins RC,Tesch GH.The Role of p38αMitogen-Activated Protein Kinase Activation in Renal Fibrosis. J Am Soc Nephml,2004, 15(2):370~379.
    20 Wang Y,Zhao MH,Zhang YK,et al.Serum IgA1 from patients with IgA nephropathy induces phosphorylation of extracellular signal-regulated kinase and proliferation of human mesangial cells. Natl Med J China, 2002,82(20):1406~1409. 王悦,赵明辉,章友康.等.IgA肾病患者血清IgA1活化细胞外信号调节激酶 并 诱 发 肾 小 球 系 膜 细 胞 增 殖 的 作 用 . 中 华 医 学 杂志,2002,82(20):1406~1409.
    21 王玉,李晓玫,王海燕.白介素-1β通过JNK/P38信号转导通路调控肾系膜细胞表达α-平滑肌肌动蛋白.生理学报,2002,54(3):244~250.
    22 Brigstock DR.The connective tissue growth factor/cysteine-rich 61/nephroblastoma overexpressed(CCN) family.Endocr Rev,1999,20(2): 189~206.
    23 Oemar BS, Luscher TF. Connective tissue growth factor. Friend or foe? Arterioscler Thromb Vasc Biol,1997,17(8):1483~1489.
    24 Gupta S,Clarkson MR,Duggan J.Connective tissue growth factor: potential role in glomerulosclerosis and tubulointerstitial fibrosis. Kidney Int,2000, 58(4):1389~1399.
    25 Ito Y,Kleij L,Alen J, et al.Connective tissue growth factor expression in the rat Thy1.1 model and regulation in mesangial cell and podocytes.J Am Soc Nephrol,1997,8:517A~519A..
    26 Murphy M,CodsonC,Cannons,et al.Suppression subtractive hybridization identifies high glucoseleve lsasastimulus for expression of connective tissue growth factor and other genes in human mesangial ce11s.J Biol Chem,1999,274(9):5830~5834.
    27 Frazier K, William S, Kothapall D et al. Stimulation of fibroblast cell growth matrix production, and granulation tissue formation by connective tissue growth factor. J InvesDermator,1996,107(3):404~411
    1 Cherpillod A,Moll S,Venetz JP,et al.IgA nephropathy:what you have need to know in 2005.Rev Med Suisse,2005,1(8):551~554,556.
    2 James V,Donadio,Joseph P,et al.IgA nephropathy.N Engl J Med,2002, 347(10):738~748.
    3 Ebihara I,Hirayama K,Yamamato S,et al.Th2 predominance at the single-cell level in patients with IgA nephropathy.Nephrol Dial transplant, 2001,16(9):1783~1789.
    4 Muro K,Yamagata K,Kobayashi M,et al.Usage of T cell recaptor variable segments of the beta-chain in IgA nephropathy. Nephron,2002, 92(1):56~63.
    5 Lee SM,Rao VM,Franklin WA,et al.IgA nephropathy:Morphologic predictors of progressive renal disease.Hum Pathol,1982,13(4):314~322.
    6 Katafuchi R,Kiyoshi Y,Oh Y,et al:Glomerular score as a prognosticator in IgA nephropathy: its usefulness and limitation. Clinical Nephropathy,1998, 49(1):1~8.
    7 Clarkson AR,Woodroffe AJ,Bannister KM,et al.The syndrome of IgA nephropathy.Clin Nephrol,1984,21(1):7~14.
    8 van der Boog PJ,van Kooten C,de Fijter JW,et al.Role of macro- molecular IgA in IgA nephropathy.Kidney Int,2005,67(3):813-821.
    9 Itoh A,Iwase H,Takatani T,et al.Nephrol Dial Transplant,2003, 18(6):1108~1114.
    10 Baskin B,Pettersson E,Rekola S,et al.Studies of the molecular basis of IgA production,subclass regulation and class-switch recombination in IgA nephropathy patients.Clin Exp Immunol,1996,106(3):509~517.
    11 Muro K,Yamagata K,Kobayashi W, et al.Usage of T cell receptor variable segments of the Beta-chain in IgA nephropathy.Nephron,2002,92 (1):56~63.
    12 Sato M,Haizuka H,Asakura H.Relationship between serum IgA levels and CD4 subsets in IgA nephropathy. Nephron,1994,68(1):20~24.
    13 Chintalacharuvu SR,Nagy NU,Sigmund N,et al.T cell cytokines determine the severity of experimental IgA nephropathy by regulating IgA glycosylation. Clin Exp Immunol,2001,126(2):326~333.
    14 Nogaki F,Muso E,Kobayashi I,et al.Nephrol Dial Transplant,2000, 15(8):1146~1154.
    15 王淑岩,施广霞,赵久阳,等.T细胞亚群及其细胞因子在原发性肾小球病中的变化.上海免疫学杂志,2002,22(6):402~404.
    16 Furusu A,Miyazaki M,Koji T,et al.Involvement of IL-4 in human glomerulonephritis:an in situ hybridization study of IL-4mRNA and IL-4 receptor mRNA.J Am Soc Nephrol,1997,8(5):730~741.
    17 Lai KN,Ho RT,Lai CK,et al.Imcrease of both circulatingTh1and Th2T lymphocyte subsets in IgA nephropathy.Clin Exp immunol,1994,96(1): 116~121.
    18 Yano N,Endoh M,Nomoto Y,et al.Phenotypic characterization of cytokine expression in patients with IgA nephropathy.J Clin Immunol, 1997,17(5):396~403.
    19 Yano N,EndohM,Naka R,et al.Altered synthesis of interferon-gamma and expression of interferon-gamma receptor by peripheral blood mononuclear cells from patients with IgA nephropathy and non-IgA proliferative glomerulonephritis.J Clin Immunol,1996,16(1):71~79.
    1 DENG SL,ZHENG SZ,YIN HL,et al.Clinical pathological features of pathogeny in 45 hemateria patient.China Journal of Modern Medicine, 2003,13(17):91~92.
    2 邹万忠 . 肾活检病理诊断标准指导意见 . 中华肾脏病杂志 ,2001, 17(4):270~275. ZOU WZ.Directions opinions for pathologic diagnositic criteria in renal biopsy.Chinese Journal of Nephrology,2001,17(4):270~275.
    3 姜傥,胡嫒芳,关伟明.肾小管间质容量改变在狼疮性肾炎中的意义.中华肾脏病杂志,1995,11(5):261~264. JIANG T,HU YF,GUAN WM.Alteration of tubulointerstitial Volume in lupus nephritis. Chinese Journal of Nephrology,1995,11(5):261~264.
    4 Muller GA,Zeisberg M and Strutz F.The importance of tubulo-interstitial damage in progressive renal disease.Nephrol Dial Transplant,2000,15 (suppl6):76~77.
    5 陈庆海,府伟灵. 尿微量蛋白检测及临床应用的研究进展.国外医学临床生物化学与检验学分册,2002,23(3):178~180. CHEN QH,FU WL.The development and progression of urinary small protein detection and clinical application. Clinical Biochemistry and Laboratory Medicine,Foreign Medical Sciences,2002,23(3):178~180.
    6 陈强,胡伟新,王生余,等.尿视黄醇结合蛋白判断肾小管-间质损伤的临床意义.肾脏病与透析肾移植杂志,2001,10(5):406~410. CHEN Q,HU WX,WANG SY,et al.The significance of urinary retinol binding protein with tubular-interstitial injure.Chinese Journal of Nephrology Dialysis & Transplantion,2001,10(5):406~410.
    7 朱立华.肾脏疾病的生化、免疫检测技术进展.中华检验医学杂志,2002, 25(5):306~308. ZHU LH. The progression of biochemistry and immunodetection technique in kidney disease.Chinese Journal of Laboratory Medicine, 2002,25(5):306~308.
    8 Coren MP,Wrighl RK.Two automated procedures for N-acetyl-β-D- glocosaminidase determiniation evaluated for detection of drug-induced tubular nephrotoxicity.Clin Chem,1998,32(10):2052~2054.
    9 罗伟文,陈向前.黄芪注射液治疗慢性肾小球肾炎蛋白尿的临床观察.中华肾脏病杂志,2000,16(3):189. LUO WW,CHEN XQ.Chinese Journal of Nephrology,2002;16(3): 189.
    10 夏春英,陈力,孟羽贤.黄芪对慢性肾炎的红细胞免疫功能及 IL-6 的影响.中国中医药科技,1997,4(5):263. XIA CY,CHEN L,MENG YX.Effect study of Astragalus injection on red cellular immune function and IL-6 in patient with chronic nephritis. Chinese Journal of Traditional Medical Science and Technology,1997,4 (5):263.
    11 李丽英,王海燕,朱世乐,等.黄芪当归对肾病综合征鼠肝白蛋白的表达作用.中华医学杂志,1995,75(5):276~279. LI LY,WANG HY,ZHU SL.et al.The effects on expressing of hepatoalbumin in rats with nephrotic syndrome by Astragalus-Angelica mixture.Chinese Medical Journal,1995,75(5):276~279.
    12 李丽英,王海燕.黄芪当归对肝脏和肾脏功能的保护作用.中华肾脏病杂志,1995,11(6):372~373.
    13 余凌,张俊峰,李惊子,等.黄芪当归合剂防治肾病综合征鼠进行性肾小管间质损伤.中华肾脏病杂志,2000,16(5):282~286. YU L,ZHANG JF,LI JZ,et al.Astragalus and Angelica retard the progressive tubulointerstitial lesions in puromycin nephropathy.Chinese Journal of Nephrology,2000,16(5):282~286.
    14 施 萍 , 李 正 . 探 讨 黄 芪 注 射 液 对 蛋 白 尿 的 影 响 . 实 用 医 技 杂志,2005,12(2):455~456.
    SHI P,LI Z.To probe the effects on treating proteinuria by astragalus injection. Journal of Practical Medical Techniques,2005,12(2B):455~456.
    1 Jin H,Axtell M J,Dahlbeck D,et al.NPK1,NPK1 and MEKK1-like Mitogen-Activated Protein Kinase Kinase Kinase,Regulates Innate Immunity and Development in Plants.Devel Cell,2002,3(2):291~297.
    2 Hans JS,Michael JW.Mitogen-Activated Protein Kinases:Specific Messages from Ubiquitous Messengers.Mol Cell Biol,1999,19(4):2435~44.
    3 Brewster JL,De Valoir T,Dwyer NG,et al.An osmosensing singnal transduction pathway in yeast.Science,1993,259(5099):1760~1763.
    4 Chang LF,Karin M.Mammalian MAP kinasc signaling cascades Nature,2001,410(6824):37~40.
    5 Pearson G,Rohinson F,Gibson TB,et al.Mitogen-activated protein (MAP) kinase pathways:Regulation and physiological functions.Endocr Rev, 2001,22:153~183.
    6 Ganiatsas S,Kwee L,Fujiwara Y,et a1.SEKl deficiency reveals mitogen- activated protein kinase cascade crossregdation and leads to abnormai hepatogenesis,Pros Natl Acad Sci USA,1998,95:6881~6886.
    7 张梅,唐嘉薇,李晓玫.P38丝裂素活化蛋白激酶信号转录对 IL-1β 由导肾小管细胞转分化的影响.中华医学杂志,2003,83(13):1161~1165.
    8 Obata T,Brown GE,Yaffe MB.MAP kinase pathways activated by stress: the p38 MAPK pathway.Crit.Care Med,2000,28(S4):N67~N77.
    9 Omori S,Hida M,Ishikura K,et al. Expression of mitogen-activated protein kinase family in rat renal development.Kidney Int,2000,58(1):27~37.
    10 Stambe C,Atkins RC,Hill PA,et al.Activation and cellular localization of the p38 and JNK MAPK pathways in rat crescentic glomerulonephritis. Kidney Int,2003,64(6):2121~2132.
    11 Dai C,Yang J W,Liu Y H.Transforming growth factor-β1 potentiates renal tubular epithelial cell death by a mechanism independent of Smad signaling.J Biol Chem,2003,278(14):12537~12545.
    12 Wang L,Ma R,Flavell RA,et al.Requirement of mitogen actived protein kinase kinase 3 (MKK3) for activation of p38alpha and p38delta MAPK isoforms by TGF-beta 1 in murine mesangial cells. J Biol Chem,2002, 277(49):47257~47262.
    13 Chin BY,Mohsenin A,Li SX,et al.Stimulation of pro-alpha(1)(I) collagen by TGF-beta(1) in mesangial cells: Role of the p38 MAPK pathway.Am J Phyaiol Renal Physiol,2001,280:F495~504.
    14 Stambe C,Atkins RC,Tesch GH.The Role of p38αMitogen-Activated Protein Kinase Activation in Renal Fibrosis.J Am Soc Nephml,2004, 15(2):370~379.
    15 De Borst MH,Navis G,de Boer RA,et al.Specific MAP-Kinase Blockade Protects against Renal Damage in Homozygous TGR(mRen2)27 Rats. LabInvest,2003,83(12):1761~1770.
    16 Sekine S,Nitta K,Uchida K,et al.Possible involvement of mitogen- activated protein kinase in the angiotensin II-induced fibronectin synthesis in renal interstitial fibroblasts.Arch Biochem Biophys,2003,415(1):63~68.
    17 Matsuda M,Shikata K,Makino H,et al.Glomerular expression of macrophage colony-stimulating factor and granulocyte-macrophage colony-stimulating factor in patients with various forms of glomerulonephritis.Lab Invest,1996,75(3):403~412.
    18 王玉,李晓玫,王海燕.白介素-1β通过JNK/p38信号转导通路调控肾系膜细胞表达 α-平滑肌肌动蛋白.生理学报,2002,54(3):244~250.
    19 Groma V.Demonstration of collagen type VI and alpha-smooth muscle actin in renal fibrotic injury in man.Nephrol Dial Transplant,1998,13(2): 305~312.
    20 Komman M,Ishiwata T,Kleeff J,et al. Fas and Fas-ligand expression in human pancreatic cancer. Ann Sung,2000,231(3):368~379.
    21 McGinn S,Saad S,Poronnik P.High glucose-mediated effects on endothelial cell proliferation occur via p38 MAP kinase Am J Physiol Endocrinol Metab.2003,285(4):E708~717.
    1 Jones CL,Bush S,Post M,et al.Renal extracellular matrix accumulation on acute puromycin aminonucleoside nephrosis in rats.Am J Pathol,1992,41: 1381~1396.
    2 Taft JL,Nolan CJ,Yeung SP,et al.Clinical and histological correlations of decline in renal function in diabetic patients with proteinuria. Diabetes, 1994,43(8):1046~1051.
    3 Strutz F,Zeisberg M,Renziehausen A,et al.TGF-β1 induces proliferation in human renal fibroblasts via induction of basic fibroblast growth factor (FGF-2).Kidney Int,2001,59(2):579~292.
    4 Goumenos DS,Tsamandas AC,EI-Nahas AM,et al.A poptosis and myofi- broblast expression in human glomerular disease:a possible link with transforming growth factor-beta-1. Nephron,2002,92(2),287~296.
    5 Sommer M,Eismann U,Deuther-Conrad W,et al.Time course of cytokine mRNA expression in kidneys of rats with unilateral ureteral obstruction.Nephron,2000,84(1):49~57.
    6 Branton MH,Kopp JB.TGF-beta and fibrosis.Microbes Infect,1999,1(15): 1349~1365.
    7 Han DC,Isono M,Hoffman BB,et al.High glucosestimulates proli-feration and collagen type 1 synthesis in renal cortical fibroblasts: mediation by auto-crine activation ofTGF-beta.J Am Soc Nephrol,1999,10(9):1891~1899.
    8 Wolf G,Ziyadeh FN.Molecular mechanisms of diabetic renal hypertrophy. Kidney Int,1999,56(2):393~405.
    9 Dai C,Yang J,Liu Y.Transforming growth factor-beta1 potentiates renal tubular epithelial cell death by amechanism independent of Smads signaling.J Biol Chem,2003,278(14):12537~12545.
    10 Serini G,Bochaton-piallat ML,Ropraz P,et al.The fibronectin domain ED-A is crucial for myofibroblastic phenotype induction by transforming growth factor-β1.J Cell Biol,1998,142(3):873~881.
    11 Ten Dijke P,Goumans MJ,Itoh F,et al.Regulation of cell proliferation by Smad proteins.J Cell Physiol,2002,191(1):1~16.
    12 Yang J,Liu Y.Dissection of key events in tubular epithelial to myofibro-blast transition and its implications in renal interstitial fibrosis. Am J Pathol,2001,159:1465~1475.
    13 Rastaldi MP,Ferrario F,Giardino L,et al.Epithelial-mesenchymal transition of tubular epithelial cells in human renal biopsies.Kidney Int,2002,62(1): 137~146.
    14 Strutz F,Zeisberg M,Ziyadeh FN,et al.Role of basic fibroblast growth factor-2 in epithelial-mesenchymal transformation.Kidney Int,2002,61(5): 1714~1728.
    15 Cheng S,Lovett DH.Gelatinase A.(MMP-2) is necessary and sufficient for renal tubular cell epithelial-mesenchymal transform- ation. Am J Pathol, 2003,162:1937~1949.
    16 Lan HY,Mu W,Tomita N,et al.In hibition of renal fibrosis by gene transfer of inducible Smad7 using ultrasound-microbubble system in rat UUO model.J Am Soc Nephrol,2003,14(6):1535~1548.
    17 Fan JM,Huang XR,Ng YY,et al.Interleukin-1 induces tubular epithelial- myofibroblast transdifferentiation through a transforming growth factor-beta1-dependent mechanism in vitro. Am J Kidney Dis,2001, 37:820~831.
    18 Peinado H,Quintanilla M,Cano A.Transforming growth factorβ-1 induces snail transcription factor in epithelial cell lines: mechanisms for epithelialmesenchymal transitions.J Biol Chem,2003,278(23):21113~21123.
    19 Li Y,Yang J,Dai C,et al.Role for integrin-linked kinase in mediating tubular epithelial to mesenchymal transition and renal interstitial fibrogenesis.J Clin Invest,2003,112(4):503~516.
    20 Tian YC,Fraser D,Attisano L,et al.TGF-β1-mediated alteration of renal proximal tubular epithelial cell phenotype.Am J Physiol Renal Physiol, 2003,285(1):F130~142.
    21 Wagner C,Viedt C,Burget A,et al.Transforming growth factor bera 1 with human glomerular epithelial cells in culture:opposite effects on synthesis of matrix proteins and on urokinase plasminogen activator.J Mol Med,1996,74(3):149~154.
    22 Geleilete TJ,Melo GC,Costa RS,et al.Role of myofibroblasts,macrophages, transforminggrowth factor-beta endothelin,angiotensin II,and fibronectin in the progression of tubulointerstitial nephritis induced by gentamicin.J Nephrol,2002,15(6):633~642.
    23 王伟铭,姚建,石蓉等.转化生长因子 β1 对肾间质成纤维细胞胶原表达的影响.中华肾脏病杂志,1999,15:343~346.
    24 Isaka Y,Tsujie M,Ando Y,et al.Transforming growth factor-β1 antisense oligodeoxynucleotides block interstitial fibrosis in unilateral ureteral obstruction.Kidney Int,2000,58:1885~1892.
    25 O.Donnell MP.Renal tubulointerstitial fibrosis: new thoughs on its development and progression.Postgrad Med,2000,108:159~172.
    26 Yamamoto T,Noble NA,Cohen AH,et al.Expression of TGF-β isoforms in human glomerular diseases. Kidney Int,1996,49:461~469.
    27 Schnaper H,Hayashida T,Hubchak SC,et al.TGF-beta signal transduction and mesangial cell fibrogenesis. Am J Physiol Renal Physiol,2003,284 (2):F243~252.
    28 Kasuga H,Ito Y,Sakamoto S,et al.Effects of anti-TGF-beta type II receptor antibody on experimental glomerulo nephritis.Kidney Int,2001,60(5): 1745~1755.
    29 Ogata Y,Ishidoya S,Fukuzaki A,et al.Upregulated expression oftransforming growth factor-beta,type IV collagen,and plasminogen activator inhibitor-1 mRNA are decreased after release of unilateral ureteral obstruction.Tohoku J Exp Med,2002,197(3):159~168.
    30 Chen Y,BlomI E,Sa S,et al.CTGF expression in mesangial cells: involvement of SMADs,MAP kinase,and PKC.Kidney Int,2002,62 (4):1149~1159.
    31 Poncelet AC,Schnaper HW.Spl and Smad proteins cooperate to mediate transforming growth factor-β1-induced alpha2(I) collagen expression in human glomerular mesangial cells. J Biol Chem,2001,276(10):6983~6992.
    32 Kanamaru Y,Nakao A,Tanaka Y,et al.Involvement of p300 in TGF-β/ Smad-pathway-mediated alpha2(I) collagen expression in mouse mesangial cells.Nephron Exp Nephrol,2003,95(1):e36~42.
    33 Chin BY,Mohsenin A,Li SX,et al.Stimulation of pro-alpha(1)(I) collagen by TGF-β(1) in mesangial cells:role of the p38MAPK pathway. Am J Physiol Renal Physiol,2001,280(3):F495~504.
    34 Mezzano SA,Drouguett MA,Burgos ME,et al.Overpexpression of chemo-kines,fibrogenic cytokines, and myofibroblasts in human membranous nephropathy.Kidney Int,2000,57:147~158.
    35 Tsao T,Fawcett J,Fervenza FC,et al.Expression of insulin-like growth factor-I and transforming factor-β in hypokalemic nephropathy in the rat.Kidney Int,2001,59(1):96~105.
    36 Goumenos DS,Tsakas S,EI NahasAM,et al.Transforming growth factor-β(1) in the kidney and urine of patients with glomerular disease and pro-teinuria.Nephrol Dial Transplant,2002,17(12):2145~2152.
    37 Goumenos DS,Tsamandas AC,Oldroyd S,et al.Transforming growth factor-β(1) and myofibroblasts: a potential pathway towards renal scaring in human glomerular disease. Nephron,2001,87(3):240~248.
    38 Rodgers KD,Rao V,Meehan DT,et al.Monocytes may promote myofibroblast accumulation and apoptosis in Alport renal fibrosis.Kidney Int,2003,63(4):1338~1355.
    39 Oemar BS,Luscher TF.Connective tissue growth factor: friend or foe? Arterioscler Thromb Vasc Biol,1997,17(8):1483~1489.
    40 Querfeld C,Sollberg S.Huerkamp C,et al.Pseudoscleroderma associated with lung cancer:correlation of collagen type 1 and connective tissue growth factor gene expression.Br J Dermatol,2000,142(6):1228~1233.
    41 Suzuki D,Toyoda M,Umezono T,et al.Glomerular expression of connective tissue growth factor mRNA in various renal diseases. Nephrology,2003, 8(2):92~97.
    42 Kanemoto K,Usui J,Tomari S,et al.Connective tissue growth factor parti- cipates in scar formation of crescentic glomerulonephritis. Laboratory Investigation,2003,83(11):1615~1625.
    43 Badid C,Vinccm M,Fouque D,et al.Myofibroblast: a prognostic marker and target cell in progressive renal disease.Renal Fail,2001,23(3-4):543~549.
    44 Abraham DJ,Shiwen X,Black CM,et al.Tumor necrosis factor alpha suppersses the induction of connective tissue growth factor by transforming growth factor beta in normal and scleroderma fibroblasts.J Biol Chem,2000,275(20):15220~15225.
    45 Blom IE,van-Dijk AJ,Wieten L,et al.In vitro evidence for differential involvement of CTGF,TGF-beta,and PDGF-BB in mesangial response to injury. Nephrol Dial Transplant,2001,16(6):1139~1148.
    46 Duncan MR,Frazier KS,Abramson S,et al.Connective tissue growth factor mediates transforming growth factor bera-induced collagen synthesis: down regulation by cAMP.FASEB J,1999,13(13):1774~1786.
    47 Kothapalli D,Hayashi N,Grotendorst GR.Inhibition of TGF-beta- stimulated CTGF gene expression and anchorage-independent growth by cAMP identifies a CTGF-dependent restriction point in the cell cycle. FASEBJ,1998,12(12):1151~1161.
    48 Ricupero DA,Rishikof DC,Kuang PP,et al.Regulation of connective tissue growth factor expression by prostaglandin E. Am J Physiol,1999,227 (6Pt1):1165~1171.
    49 Suzuma K,Naruse K,Suzuma I,et al.Vascular endothelial growth factorinduces expression of connective tissue growth factor via KDR,FItl,and phosphatidylinositol 3-kinase–Akt–dependent pathways in retinal vascular cells.J Biol Chem,2000,275(52):40725~40731.
    50 Caramori ML,Mauer M.Diabetes and nephropathy. Curr Opin Nephrol Hypertents,2003,12(3):273~282.
    51 Wang S,Denichilo M,Brubaker C,et al.Connective tissue growth factor in tubulointerstitial injury of diabetic nephropathy.Kidney International, 2001,60(1):96~105.
    52 Frazier KS,Paredes A,Dube P,et al.Connective tissue growth factor expression in the rat remnant kidney model and association with tubular epithelial cells undergoing transdifferentiation.Vet Pathol,2000,37(4): 328~335.
    53 Riser BR,Cortes P.Connective tissue growth factor and its regulation:a new element in diabetic glomerulosclerosis.Ren Fail,2001,23(3-4): 459~470.
    54 Gary RG.Connective tissue growth factor:a nediator of TGF-beta actionon fibroblasts.Cytokine & Growth Factor Reviews,1997,8(3):171~179.
    55 Gore-Hyer E,Shegogue D,Markiewicz M,et al.TGF-beta and CTGF have overlapping and distinct fibrogenic effects on human renal cells. Am J Physiol Renal Physiol,2002,283(4):F707~716.
    56 Yokoi H,Sugawara A,Mukoyama M,et al.Role of connective tissue growth factor in profibrotic action of transforming growth factor-beta:a potential target for preventing renal fibrosis.Am J Kidney Dis,2001,38(4Suppl 1):S134~138.
    57 Gupta S,Clarkson MR,Duggan J,et al.Connective tissue growth factor: potential role in glomeruloselerosis and tubulointerstitial fibrosis. Kidney Int,2000,58(4):1389~1399.
    58 Zhang C, Meng X, Zhu Z, et al. Role of connective tissue growth factor in renal tubular epithelial-myofibroblast transdifferentiation and extracellular matrix accumulation in vitro. Life Sci,2004,75(3):367~379.
    59 Frazier K,Williams S,Kothapalli D,et al.Stimulation of fibroblast cell growth,matrix production,and granulation tissue formation by connectivetissue growth factor. J Invest Dermatol,1996,107:404~411.

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