Inflammation and EMT: An alliance towards organ fibrosis and cancer progression

EMBO Molecular Medicine

Volumn 1, Issue 6-7, 2009, Pages 303-314

  López Nouoa, Jose Miguel ^a   Nieto, M Angela ^b  

^a UNIVERSITY OF SALAMANCA   (Spain)

^b INSTITUTO DE NEUROCIENCIAS   (Spain)

Author keywords

Epithelial mesenchymal transition; Inflammation; TGF TNF NF KB

Indexed keywords

ANGIOTENSIN II; BETA CATENIN; CADHERIN; CADHERIN 16; COLLAGEN TYPE 1; GELATINASE A; GELATINASE B; HYPOXIA INDUCIBLE FACTOR; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTEGRIN LINKED KINASE; NEUTRALIZING ANTIBODY; OSTEOGENIC PROTEIN 1; PROTEIN INHIBITOR; REACTIVE OXYGEN METABOLITE; RHO GUANINE NUCLEOTIDE BINDING PROTEIN; SMAD PROTEIN; TRANSCRIPTION FACTOR SNAIL; TRANSFORMING GROWTH FACTOR BETA RECEPTOR; TRANSFORMING GROWTH FACTOR BETA RECEPTOR ANTIBODY; TRANSFORMING GROWTH FACTOR BETA RECEPTOR INHIBITOR; TRANSFORMING GROWTH FACTOR BETA1; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; UVOMORULIN;

ANTIINFLAMMATORY ACTIVITY; BASEMENT MEMBRANE; BREAST CARCINOMA; CANCER ASSOCIATED FIBROBLAST; CANCER CELL; CANCER GROWTH; CANCER INVASION; CELL MIGRATION; CELL SHAPE; CELL STRUCTURE; CLINICAL TRIAL; CYTOKINE RELEASE; EMBRYO DEVELOPMENT; ENZYME ACTIVATION; EPIGENETICS; EPITHELIAL MESENCHYMAL TRANSITION; EXTRACELLULAR MATRIX; FIBROBLAST; FIBROSIS; GENE EXPRESSION; GENOTOXICITY; GLOMERULONEPHRITIS; HEART MUSCLE FIBROSIS; HUMAN; HYPOXEMIA; INFLAMMATION; KIDNEY CARCINOMA; KIDNEY DISEASE; KIDNEY FIBROSIS; LIVER FIBROSIS; LUNG FIBROSIS; METASTASIS; MICROENVIRONMENT; MYOFIBROBLAST; OBSTRUCTIVE NEPHROPATHY; ORGANOGENESIS; OXIDATIVE STRESS; PRIORITY JOURNAL; PROTEIN EXPRESSION; RENIN ANGIOTENSIN ALDOSTERONE SYSTEM; REVIEW; RNA INTERFERENCE; SIGNAL TRANSDUCTION; TISSUE DIFFERENTIATION; TUMOR ASSOCIATED LEUKOCYTE; UNILATERAL URETERAL OBSTRUCTION; URETER OBSTRUCTION;

ANIMALS; DISEASE PROGRESSION; FIBROSIS; HUMANS; INFLAMMATION; NEOPLASMS; NEOPLASTIC PROCESSES; TRANSFORMING GROWTH FACTOR BETA1;

EID: 70450142560     PISSN: 17574676     EISSN: 17574684     Source Type: Journal    
DOI: 10.1002/emmm.200900043     Document Type: Review

References (122)

1. Acloque H, Adams M, Fishwick K, Bronner-Fraser M, Nieto MA (2009) Epithelial-mesenchymal transitions: the importance of changing cells' state in development and disease. J Clin Invest 119: 1438-1449
2. Acloque H, Thiery JP, Nieto MA (2008) The physiology and pathology of the epithelial to mesenchymal transition. EMBO Rep 9: 322-326
3. Adorno M, Cordenonsi M, Montagner M, Dupont S, Wong C, Hann B, Solari A, Bobisse S, Rondina MB, Guzzardo V,etal(2009) A mutnat-p53/Smad complex opposes p63 to empower TGFβ-induced metastasis. Cell 177: 87-98
4. Apolant H (1906) Die epithelialen Geschwiilste der Maus. Arb Konigl Inst Exp Ther 1: 7-62
5. Baan C, van Gelder T, Peeters A, Mol W, Niesters H, Weimar W, IJzermans J (2003) Living kidney donors and hypoxia-inducible factor-1alpha. Transplantation 75: 570-571
6. Bachelder RE, Yoon SO, Franci C, de HerrerosAG, Mercurio AM (2005) Glycogen synthase kinase-3 is an endogenous inhibitor of Snail transcription: implications for the epithelial-mesenchymal transition. J Cell Biol 168: 29-33
7. Barbera MJ, Puig I, Domfnguez D, Julien-Grille S, Guaita-Esteruelas S, Peiro S, Baulida J, Francf C, Dedhar S, Larue L, et al(2004) Regulation of Snail transcription during epithelial to mesenchymal transition of tumor cells. Oncogene 23: 7345-7354
8. Barrallo-Gimeno A, Nieto MA (2005) The Snail genes as inducers of cell movement and survival: implications in development and cancer. Development 132: 3151-3161
9. Bhowmick NA, Ghiassi M, Bakin A, Aakre M, Lundquist CA, Engel ME, Arteaga CL, Moses HL (2001) Transforming growth factor-beta1 mediates epithelial to mesenchymal transdifferentiation through a RhoA-dependent mechanism. Mol Biol Cell 12: 27-36
10. Blackwell TS, Christman JW (1997) The role of nuclear factor-kappa B in cytokine gene regulation. Am J Respir Cell Mol Biol 17: 3-9
11. Bottaro DP, Liotta LA (2003) Out of air is not out of action. Nature 423: 593-595
12. Bottinger EP (2007) TGF-beta in renal injury and disease. Semin Nephrol 27: 309-320
13. Boutet A, De Frutos CA, Maxwell PH, Mayol MJ, Romero J, Nieto MA (2006) Snail activation disrupts tissue homeostasis and induces fibrosis in the adult kidney. EMBO J 25: 5603-5613
14. Brabletz T, Jung A, Reu S, Porzner M, Hlubek F, Kunz-Schughart LA, Knuechel R, Kirchner T (2001) Variable beta-catenin expression in colorectal cancers indicates tumor progression driven by the tumor environment. Proc Natl Acad Sci USA 98: 10356-10361
15. Bruna A, Darken RS, Rojo F, Ocana A, Penuelas S, Arias A, Paris R, Tortosa A, Mora J, Baselga J, et al(2007) High TGFbeta-Smad activity confers poor prognosis in glioma patients and pomotes cell proliferation depending on the methylation of the PDGF-B gene. Cancer Cell 11: 147-160
16. Bukholm IK, Nesland JM, B0rresen-Dale AL (2000) Re-expression of E-cadherin, alpha-catenin and beta-catenin, but not of gamma-catenin, in metastatic tissue from breast cancer patients. J Pathol 190: 15-19
17. Chevalier RL, Forbes MS, Thornhill BA (2009) Ureteral obstruction as a model of renal interstitial fibrosis and obstructive nephropathy. Kidney Int 75: 1145-1152
18. Chevalier RL (2006) Obstructive nephropathy: towards biomarker discovery and gene therapy. Nat Clin Pract Nephrol 2: 157-168
19. Chua HL, Bhat-Nakshatri P, Clare SE, Morimiya A, Badve S, Nakshatri H (2007) NF-kappaB represses E-cadherin expression and enhances epithelial to mesenchymal transition of mammary epithelial cells: potential involvement of ZEB-1 and ZEB-2. Oncogene 26: 711-724
20. Chua KN, Ma J, Thiery JP (2008) Targeted therapies in control of EMT in carcinoma and fibrosis. Drug Discov Today 4: 261-267
21. Condeelis J, Pollard JW (2006) Macrophages: obligate partners fro tumor cell migration, invasion and metastasis. Cell 124: 263-266
22. Condeelis J, Segall JE (2003) Intravital imaging of cell movement in tumours. Nat Rev Cancer 3: 921-930
23. Cordon-Cardo C, Prives C (1999) At the crossroads of inflammation and tumorigenesis. J Exp Med 190: 1367-1370
24. Dehayes F, Nahmias C (2005) Angiotensin receptors: a new role in cancer? Trends Endocrinol Metab 16: 293-299
25. Devescovi V, Leonardi E, Ciapetti G, Cenni E (2008) Growth factors in bone repair. Chir Organi Mov 92: 161-168
26. Diamond JR (1995) Macrophages and progressive renal disease in experimental hydronephrosis. Am J Kidney Dis 26: 133-140
27. Diamond JR, Ricardo SD, Klahr S (1998) Mechanisms of interstitial fibrosis in obstructive nephropathy. Semin Nephrol 18: 594-602
28. Ding G, Pesek-Diamond I, Diamond JR (1993) Cholesterol, macrophages, and gene expression of TGF-,81 and fibronectin during nephrosis. Am J Physiol Renal Fluid Electrolyte Physiol 264: F577-F584
29. Dong R, Wang Q, He XL, Chu YK, Lu JG, Ma QJ (2007) Role of nuclear factor kappa B and reactive oxygen species in the tumor necrosis factor-alpha-induced epithelial-mesenchymal transition of MCF-7 cells. Braz J Med Biol Res 40: 1071-1078
30. Esteban V, Ruperez M, Vita JR, Lfopez ES, Mezzano S, Plaza JJ, Egido J, Ruiz-Ortega M (2003) Effect of simultaneous blockade of AT1 and AT2 receptors on the NFkappaB pathway and renal inflammatory response. Kidney Int Suppl S33-S38
31. Esteban V, Lorenzo O, Rupferez M, Suzuki Y, Mezzano S, Blanco J, Kretzler M, Sugaya T, Egido J, Ruiz-Ortega M (2004) Angiotensin II, via AT1 and AT2 receptors and NF-kappaB pathway, regulates the inflammatory response in unilateral ureteral obstruction. J Am Soc Nephrol 15: 1514-1529
32. Evans AJ, Russell RC, Roche O, BurryTN, Fish JE, Chow VW, Kim WY, Saravanan A, Maynard MA, Gervais ML, et al(2007) VHL promotes E2 box dependent E-cadherin transcription by HIF-mediated regulation ofSIP1 and snail. Mol Biol 27: 157-169
33. Ferenbach D, Kluth DC, HughesJ (2007) Inflammatory cells in renal injury and repair. Semin Nephrol 27: 250-259
34. Frangogiannis NG (2008) The immune system and cardiac repair. Pharmacol Res 58: 88-111
35. Gharaee-Kermani M, Hu B, Phan SH, Gyetko MR (2009) Recent advances in molecular targets and treatment of idiopathic pulmonary fibrosis: focus on TGFbeta signaling and the myofibroblast. Curr Med Chem 16:1400-1417
36. Gloire G, Legrand-Poels S, Piette J (2006) NF-kappaB activation by reactive oxygen species: fifteen years later. Biochem Pharmacol 72: 1493-1505
37. Gorelik L, Flavell RA (2000) Abrogation of TGF-13 signaling in T cells leads to spontaneous T cell differentiation and autoimmune disease. Immunity 12: 171-181
38. Grande MT, Lopez-Novoa JM (2009) Fibroblast activation and myofibroblast generation in obstructive nephropathy. Nat Rev Nephrol 5: 319-328
39. Gressner OA, Rizk MS, Kovalenko E, Weiskirchen R, Gressner AM (2008) Changing the pathogenetic roadmap of liver fibrosis? Where did it start, where will it go? J Gastroenterol Hepatol 23: 1024-1035
40. Hay ED (1968) Organization and fine structure of epithelium and mesenchyme in the developing chick embryo. In: Epithelial-Mesenchymal Interactions, Fleischmajer R and Billingham RE (eds), Baltimore, MD, USA: Williams &Wilkins Co: pp 31-55
41. Hay ED (1990) Role of cell-matrix contacts in cell migration and epithelial-mesenchymal transformation. Cell Differ Dev 32: 367-375
42. Hay ED (1991) Collagen and other matrix glycoproteins in embryogenesis. In: Cell Biology of Extracellular Matrix, Hay ED (ed.), New York: Plenum Press: pp 419-462
43. Hegarty NJ, Young LS, Kirwan CN, O'Neill AJ, Bouchier-Hayes DM, Sweeney P, Watson RW, Fitzpatrick JM (2001) Nitric oxide in unilateral ureteral obstruction: effect on regional renal blood flow. Kidney Int 59:1059-1065
44. Higgins DF, Kimura K, Bernhardt WM, Shrimanker N, Akai Y, Hohenstein B, Saito Y, Johnson RS, Kretzler M, Cohen CD, et al(2007) Hypoxia promotes fibrogenesis in vivo via HIF-1 stimulation of epithelial-to-mesenchymal transition. J Clin Invest 117: 3810-3820
45. Huber MA, Azoitei N, Baumann B, Grunert S, SommerA, Pehamberger H, Kraut N, Beug H, Wirth T (2004) NF-kappaB is essential for epithelial- mesenchymal transition and metastasis in a model of breast cancer progression. J Clin Invest 114: 569-581
46. Iwano M, Plieth D, Danoff TM, et al (2002) Evidence that fibroblasts derive from epithelium during tissue fibrosis. J Clin Invest 110: 341-350
47. Jinde K, Nikolic-Paterson DJ, HuangXR,Sakai H, Kurokawa K, Atkins RC, Lan HY (2001) Tubular phenotypic change in progressive tubulointerstitial fibrosis in human glomerulonephritis. Am J Kidney Dis 38: 761-769
48. Julien S, Puig I, Caretti E, Bonaventure J, Nelles L, van Roy F, Dargemont C, de Herreros AG, Bellacosa A, Larue L (2007) Activation of NF-kappaB by Akt upregulates Snail expression and induces epithelium mesenchyme transition. Oncogene 26: 7445-7456
49. Kalluri R, Neilson EG (2003) Epithelial-mesenchymal transition and its implications for fibrosis. J Clin Invest 112: 1776-1784
50. Kalluri R, Weinberg R (2009) The basics of epithelial-mesenchymal transition. J Clin Invest 119: 1420-1428
51. Kaneto H, MorrisseyJ, KlahrS (1993) Increased expression of TGF-beta 1 mRNA in the obstructed kidney of rats with unilateral ureteral ligation. Kidney Int 44: 313-321
52. Kawada N, Moriyama T, Ando A, Fukunaga M, Miyata T, Kurokawa K, Imai E, Hori M (1999) Increased oxidative stress in mouse kidneys with unilateral ureteral obstruction. Kidney Int 56: 1004-1013
53. Karin M (2006) Nuclear factor-kappaB in cancer development and progression. Nature 441: 431-436
54. Karin M, Greten FR (2005) NF-kappaB. Linking inflammation and immunity to cancer development and progression Nat Rev Immunol 5: 749-759
55. Kim KK, Kugler MC, Wolters PJ, Robillard L, Galvez MG, Brumwell AN, Sheppard D, Chapman HA (2006) Alveolar epithelial cell mesenchymal transition develops in vivo during pulmonaryfibrosis and is regulated by the extracellular matrix. Proc Natl Acad Sci USA 103: 13180-13185
56. Kim HJ, Litzenburger BC, Cui X, Delgado DA, Grabiner BC, Lin X, Lewis MT, Gottardis MM, Wong TW, et al(2007) Constitutively active type I insulin-like growth factor receptor causes transformation and xenograft growth of immortalized mammary epithelial cells and is accompanied by an epithelial-to-mesenchymal transition mediated by NF-kappaB and snail. Mol Cell Biol 27: 3165-3175
57. Kisseleva T, Brenner DA (2008) Fibrogenesis of parenchymal organs. Proc Am Thorac Soc 5: 338-342
58. Kitamura M, Suto TS (1997) TGF-beta and glomerulonephritis: anti- inflammatory versus prosclerotic actions. Nephrol Dial Transplant 12: 669-679
59. Klahr S, Morrissey J (2002) Obstructive nephropathy and renal fibrosis. Am J Physiol Renal Physiol 283: F861-F875
60. Krishnamachary B, Zagzag D, Nagasawa H, Rainey K, Okuyama H, BaekJH, Semenza GL (2006) Hypoxia-inducible factor-1-dependent repression of E-cadherin in von Hippel-Lindau tumor suppressor-null renal cell carcinoma mediated by TCF3, ZFHX1A, and ZFHX1B. Cancer Res 66:2725-2731
61. Kudo-Saito C, Shirako H, Takeuchi T, Kawakami Y(2009) Cancer metastasis is accelerated through immunosuppression during Snail-induced EMT of cancer cells. Cancer Cell 15: 195-206
62. Kulkarni AB, Huh CG, Becker D, Geiser A, Lyght M, Flanders KC, Roberts AB, Sporn MB, Ward JM, Karlsson S (1993) Transforming growth factor 131 null mutation in mice causes excessive inflammatory response and early death. Proc Natl Acad Sci USA 90: 770-774
63. Kuwabara N,Tamada S, Iwai T,Teramoto K, Kaneda N, Yukimura T, Nakatani T, Miura K (2006) Attenuation of renal fibrosis by curcumin in rat obstructive nephropathy. Urology 67: 440-446
64. Lange-Sperandio B, Trautmann A, Eickelberg O, Jayachandran A, Oberle S, Schmidutz F, Rodenbeck B, Homme M, Horuk R, Schaefer F (2007) Leukocytes induce epithelial to mesenchymal transition after unilateral ureteral obstruction in neonatal mice. Am J Pathol 171: 861-871
65. Letterio JJ, Roberts AB (1998) Regulation of immune responses byTGF-3. Annu Rev Immunol 16: 137-161
66. Li JH, Zhu HJ, Huang XR, Lai KN, Johnson RJ, Lan HY (2002) Smad7 inhibits fibrotic effect of TGF-beta on renal tubular epithelial cells by blocking smad2 activation. J Am Soc Nephrol 13: 1464-1472
67. Li Y, Yang J, Dai C, Wu C, Liu Y (2003) Role for integrin-linked kinase in mediating tubular epithelial to mesenchymal transition and renal interstitial fibrogenesis. J Clin Invest 112: 503-516
68. Liu Y (2006) Renal fibrosis: new insights into the pathogenesis and therapeutics. Kidney Int 69: 213-217
69. Lyons JG, Patel V, Roue NC, Fok SY, Soon LL, Halliday GM, Gutkind JS (2008) Snail up-regulates proinflammatory mediators and inhibits differentiation in oral keratinocytes. Cancer Res 68: 4525-4530
70. Ma LJ, Yang H, Gaspert A,et al(2003) Transforming growth factor-beta- dependent and -independent pathways of induction of tubulointerstitial fibrosis in beta6 (7/7) mice. Am J Pathol 163: 1261-1273
71. Mantovani A, Allavena P, Sica A, Balkwill F (2008) Cancer-related inflammation. Nature 454: 436-444
72. Massague J (2008) TGFb in cancer. Cell 134: 215-230
73. Masszi A, Di Ciano C, Sirokmany G, Arthur WT, Rotstein OD, Wang J, McCulloch CA, Rosivall L, Mucsi I, Kapus A (2003) Central role for Rho in TGF-beta1- induced alpha-smooth muscle actin expression during epithelial- mesenchymal transition. Am J Physiol 284: F911-F924
74. Masszi A, Fan L, Rosivall L, McCulloch CA, Rotstein OD, Mucsi I, Kapus A (2004) Integrity of cell-cell contacts is a critical regulator of TGF-beta 1-induced epithelial-to myofibroblast transition: role for beta-catenin. Am J Pathol 165: 1955-1967
75. Meldrum KK, Metcalfe P, Leslie JA, Misseri R, Hile KL, Meldrum DR (2006) TNF- alpha neutralization decreases nuclear factor-kappaB activation and apoptosis during renal obstruction. J Surg Res 131: 182-188
76. Metcalfe PD, Leslie JA, Campbell MT, Meldrum DR, Hile KL, Meldrum KK (2008) Testosterone exacerbates obstructive renal injury bystimulating TNF-alpha production and increasing proapoptotic and profibrotic signaling. Am J Physiol Endocrinol Metab 294: E435-E443
77. Misseri R, Meldrum DR, Dinarello CA, Dagher P, Hile KL, Rink RC, Meldrum KK (2005) TNF-alpha mediates obstruction-induced renal tubular cell apoptosis and proapoptotic signaling. Am J Physiol Renal Physiol 288: F406-F411
78. Micke P, Ostman A (2005) Exploring the tumour environment: cancer- associated fibroblasts as targets in cancertherapy. Expert Opin TherTargets 9: 1217-1233
79. Miyajima A, Kosaka T, Seta K, Asano T, Umezawa K, Hayakawa M (2003) Novel nuclear factor kappa B activation inhibitor prevents inflammatory injury in unilateral ureteral obstruction. J Urol 169: 1559-1563
80. Moriyama T, Kawada N, Nagatoya K, Takeji M, Horio M, Ando A, Imai E, Hori M (2001) Fluvastatin suppresses oxidative stress and fibrosis in the interstitium of mouse kidneys with unilateral ureteral obstruction. Kidney Int 59: 2095-2103
81. MorrisseyJJ, Klahr S (1997) Enalapril decreases nuclear factor kappa B activation in the kidney with ureteral obstruction. Kidney Int 52: 926-933
82. Peinado H, Quintanilla M, Cano A (2003) Transforming growth factor beta-1 induces snail transcription factor in epithelial cell lines: mechanisms for epithelial mesenchymal transitions. J Biol Chem 278: 21113-21123
83. Pikarsky E, Porat RM, Stein I, Abramovitch R, Amit S, Kasem S, Gutkovich-Pyest E, Urieli-Shoval S, Galun E, Ben-Neriah Y (2004) NF-kappaB functions as a tumour promoter in inflammation-associated cancer. Nature 431:461-466
84. Quinlan MR, Docherty NG, Watson RW, Fitzpatrick JM (2008) Exploring mechanisms involved in renal tubular sensing of mechanical stretch following ureteric obstruction. Am J Physiol Renal Physiol 295: F1-F11
85. Radisky DC, Levy DD, Littlepage LE, Liu H, Nelson CM, Fata JE, Leake D, Godden EL, Albertson DG, Nieto MA, et al(2005) Rac1b and reactive oxygen species mediate MMP-3-induced EMT and genomic instability. Nature 436: 123127
86. Ramon y Cajal S (1890) Manual de Anatomla Patologica General, Barcelona: Imprenta de la Casa Provincial de la Caridad Rastaldi MP, Ferrario F, Giardino L, Dell'Antonio G, Grillo C, Grillo P, Strutz F, MullerGA, Colasanti G, D'Amico G (2002) Epithelial-mesenchymal transition oftubular epithelial cells in human renal biopsies. KidneyInt 62: 137-146
87. Ricardo SD, Ding G, Eufemio M, Diamond JR (1997) Antioxidant expression in experimental hydronephrosis: role of mechanical stretch and growth factors. Am J Physiol 272: F789-F798
88. Rius J, Guma M, Schachtrup C, Akassaglou K, Zinkernagel AS, Nizet V, Johnson RS, Haddad GG, Karin M (2008) NF-kappaB links innate immunity to the hypoxic response through transcriptional regulation of HIF-1alpha. Nature 453: 807-811
89. Rodrfguez-Barbero A, Dorado F, Velasco S, Pandiella A, Banas B, Lopez-Novoa JM (2006) TGF-beta1 induces COX-2 expression and PGE2 synthesis through MAPK and PI3K pathways in human mesangial cells. Kidney Int 70: 901-909
90. Ruiz-Ortega M, Lorenzo O, Rupferez M, Blanco J, Egido J (2001) Systemic infusion of angiotensin II into normal rats activates nuclear factor-kappaB and AP-1 in the kidney: role of AT(1) and AT(2) receptors. Am J Pathol 158: 1743-1756
91. Ruiz-Ortega M, Rupferez M, Esteban V, Rodriguez-Vita J, Sanchez-Lopez E, Egido J (2003) Modulation of angiotensin II effects, a potential novel approach to inflammatory and immune diseases. Curr Med Chem 2: 379-394
92. Sahlgren C, Gustafsson MV, Jin S, Poellinger L, Lendahl U (2008) Notch signaling mediates hypoxia-induced tumor cell migration and invasion. Proc Natl Acad Sci USA 105: 6392-6397
93. Sato M, Muragaki Y, Saika S, Roberts AB, Ooshima A (2003) Targeted disruption of TGF-beta1/Smad3 signaling protects against renal tubulointerstitial fibrosis induced by unilateral ureteral obstruction. J Clin Invest 112: 1486-1494
94. Shi Y, Massague J (2003) Mechanisms of TGF-beta signalling from cell membrane to the nucleus Cell. 113: 685-690
95. Shull MM, Ormsby I, KierAB, Pawlowski S, Diebold RJ, Yin M, Allen R, Sidman C, Proetzel G, Calvin D, et al(1992) Targeted disruption of the mouse transforming growth factor-13 gene results in multifocal inflammatory disease. Nature 359: 693-699
96. Siegel PM, Shu W, Cardiff RD, Muller WJ, Massague J (2003) Transforming growth factor b signalling impairs Neu-induced tumorigenesis while promoting pulmonary metastasis. Proc Natl Acad Sci USA 100:8430-8435
97. Silverstein DM, Travis BR, Thornhill BA, Schurr JS, Kolls JK, Leung JC, Chevalier RL (2003) Altered expression ofimmune modulator and structural genes in neonatal unilateral ureteral obstruction. Kidney Int 64: 25-35
98. Smith JM, Stablein DM, Munoz R, Hebert D, McDonald RA(2007) Contributions of the transplant registry: the 2006 Annual Report of the North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS). Pediatr Transplant 11: 366-373
99. Strippoli R, Benedicto I, Perez Lozano ML,CerezoA, Lopez-Cabrera M,del Pozo MA (2008) Epithelial-to-mesenchymal transition of peritoneal mesothelial ells is regulated by an ERK/NF-kappaB/Snail1 pathway. Dis Model Mech 1:264-274
100. Strutz F, Zeisberg M, Ziyadeh FN, Yang CQ, Kalluri R, Muller GA, Neilson EG (2002) Role of basic fibroblast growth factor-2 in epithelial-mesenchymal transformation. Kidney Int 61: 1714-1728
101. Sullivan DE, Ferris M, Nguyen H, Abboud E, BrodyAR (2009)TNF-alpha induces TGF-beta(1) expression in lung fibroblasts at the transcriptional level via AP-1 activation. J Cell Mol Med, DOI: 10.1111/j.1582-4934.2008.00647.x
102. Sun S, NingX, Zhang Y, Lu Y, Nie Y, Han S, Liu L, Du R, Xia L, He L, et al.(2009) Hypoxia-inducible factor-1alpha induces Twist expression in tubular epithelial cells subjected to hypoxia, leading to epithelial-to- mesenchymal transition. Kidney Int 75: 1278-1287
103. Tan R, Zhang J, Tan X, Zhang X, Yang J, Liu Y (2006) Downregulation of SnoN expression in obstructive nephropathy is mediated by an enhanced ubiquitin-dependent degradation. J Am Soc Nephrol 17: 2781-2791
104. Tashiro K, Tamada S, Kuwabara N, Komiya T, Takekida K, Asai T, Iwao H, Sugimura K, Matsumura Y, Takaoka M, et al(2003) Attenuation of renal fibrosis by proteasome inhibition in rat obstructive nephropathy: possible role of nuclear factor kappaB. Int J Mol Med 12: 587-592
105. Uemura H, Ishiguro H, Ishiguro Y, Hoshino K, Takhashi S, Kubota Y (2008) Angiotensin II induces oxidative stress in prostate cancer. Mol Cancer Res 6: 250-258
106. Vega S, Morales AV, Ocana OH, Valdes F, Fabregat I, Nieto MA (2004) Snail blocks the cell cycle and confers resistance to cell death. Genes Dev 18: 1131-1143
107. Vongwiwatana A, Tasanarong A, Rayner DC, Melk A, Halloran PF (2005) Epithelial to mesenchymal transition during late deterioration of human kidney transplants: the role of tubular cells in fibrogenesis. Am J Transplant 5: 1367-1374
108. Vuruskan H, Caliskan Z, Kordan Y, Ozakin C, Yavascaoglu I, Oktay B (2005) Elevated plasma concentrations oftransforming growth factor-beta 1 in patients with unilateral ureteral obstruction. Urol Res 33: 465-469
109. Wahl SM, Hunt DA, Wakefield LM, McCartney-Francis N, Wahl LM, Roberts AB, Sporn MB (1987) Transforming growth factor type b induces monocyte chemotaxis and growth factor production. Proc Natl Acad Sci USA 84: 5788-5792
110. Wolf G (2006) Renal injury due to renin-angiotensin-aldosterone system activation of the transforming growth factor-beta pathway. Kidney Int 70: 1914-1919
111. Wolf G, Ziyadeh FN, Thaiss F, Tomaszewski J, Caron RJ, Wenzel U, Zahner G, Helmchen U, Stahl RA (1997) Angiotensin II stimulates expression of the chemokine RANTES in rat glomerular endothelial cells. Role of the angiotensin type 2 receptor. J Clin Invest 100: 1047-1058
112. Wu Y, Deng J, Rychahou PG, Qiu S, Evers BM, Zhou BP (2009) Stabilization of Snail by NF-kB is required for inflammation-induced cell migration and invasion. Cancer Cell 15: 416-428
113. Yamagishi H, Yokoo T, Imasawa T, Mitarai T, Kawamura T, Utsunomiya Y (2001) Genetically modified bone marrow-derived vehicle cells site specifically deliver an anti-inflammatory cytokine to inflamed interstitium of obstructive nephropathy. J Immunol 166: 609-616
114. Yang MH, Wu MZ, Chiou SH, Chen PM, Chang SY, Liu CJ, Teng SC, Wu KJ (2008) Direct regulation of TWIST by HIF-1alpha promotes metastasis. Nat Cell Biol10: 295-305
115. Yoshino J, Monkawa T, Tsuji M, Inukai M, Itoh H, Hayashi M (2007) Snail1 is involved in the renal epithelial-mesenchymal transition. Biochem Biophys Res Commun 362: 63-68
116. Zavadil J, Bottinger EP (2005) TGF-beta and epithelial-to-mesenchymal transitions. Oncogene 24: 5764-5774
117. Zeisberg M, Hanai J, Sugimoto H, Mammoto T, Charytan D, Strutz F, Kalluri R (2003) BMP-7 counteracts TGF-b1-induced epithelial-to- mesenchymal transition and reverses chronic renal injury. Nat Med 9:964-968
118. Zeisberg M, Kalluri R (2008) Fibroblasts emerge via epithelial- mesenchymal transition in chronic kidney fibrosis. Front Biosci 13: 6991-6998
119. Zeisberg EM, Potenta SE, Sugimoto H, Zeisberg M, Kalluri R (2008) Fibroblasts in kidney fibrosis emerge via endothelial-to-mesenchymal transition. JAm Soc Nephrol 19: 2282-2287
120. Zeisberg M, Yang C, Martino M, Duncan MB, Rieder F, Tanjore H, Kalluri R (2007a) Fibroblasts derive from hepatocytes in liver fibrosis via epithelial to mesenchymal transition. J Biol Chem 282: 23337-23347
121. Zeisberg EM,Tarnavski O, Zeisberg M, Dorfman AL, McMullen JR, Gustafsson E, Chandraker A, Yuan X, Pu WT, Roberts AB, et al(2007b) Endothelial-to- mesenchymal transition contributes to cardiac fibrosis. Nat Med 13: 952-961
122. Zhou BP, DengJ,Xia W,XuJ, Li YM,Gunduz M, HungMC (2004) Dual regulation of Snail by GSK-3beta-mediated phosphorylation in control of epithelial- mesenchymal transition Nat Cell Biol. 6: 931-940