Mesenchymal transition in kidney collecting duct epithelial cells.

Progressive organ damage due to tissue scarring and fibrosis is a paradigm shared by numerous human diseases including chronic kidney disease. The purpose of this study was to confirm the hypothesis that collecting duct (CD) epithelial cells can undergo mesenchymal transition (EMT) in vitro. The mechanism by which CDs undergo EMT is complex and involves both early and late cellular events. Early events include rapid insulin-like growth factor (IGF)-induced Akt and GSK-3beta phosphorylation, associated with early disruption of E-cadherin-beta-catenin membrane colocalization, with translocation of E-cadherin to endosomes, with translocation of beta-catenin to the nucleus, and with an increase in Snail expression. Transforming growth factor-beta1, on the other hand, induced early activation of Smad3 and its translocation to the nucleus, Erk1/2 phosphorylation, and early disruption of membrane E-cadherin localization. The late consequences of these events included a phenotypic transformation of the cells to a mesenchymal morphology with associated increase in vimentin and alpha-smooth muscle actin protein expression and a decrease in total cellular E-cadherin expression, detectable as early as 24 h after stimulation.

[1]  W. Nelson,et al.  Adherens and tight junctions: structure, function and connections to the actin cytoskeleton. , 2008, Biochimica et biophysica acta.

[2]  C. Pin,et al.  The role of the type I insulin-like growth factor receptor (IGF-IR) in glomerular integrity. , 2008, Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society.

[3]  A. Tarantal,et al.  Collecting duct epithelial-mesenchymal transition in fetal urinary tract obstruction. , 2007, Kidney international.

[4]  B. Willis,et al.  TGF-β-induced EMT: mechanisms and implications for fibrotic lung disease , 2007 .

[5]  A. Mercurio,et al.  Epithelial-Mesenchymal Transition and Colorectal Cancer: Gaining Insights into Tumor Progression Using LIM 1863 Cells , 2007, Cells Tissues Organs.

[6]  E. Bottinger.  TGF-β in renal injury and disease , 2007 .

[7]  Adrian V. Lee,et al.  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-κB and Snail , 2007, Molecular and Cellular Biology.

[8]  J. Jimenez-Heffernan,et al.  Epithelial-to-mesenchymal transition of the mesothelial cell--its role in the response of the peritoneum to dialysis. , 2006, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[9]  E. Simpson,et al.  Als2-deficient mice exhibit disturbances in endosome trafficking associated with motor behavioral abnormalities. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[10]  A. E. El Nahas,et al.  An IGF-I antagonist does not inhibit renal fibrosis in the rat following subtotal nephrectomy. , 2006, American journal of physiology. Renal physiology.

[11]  M. Jinnin,et al.  Characterization of SIS3, a Novel Specific Inhibitor of Smad3, and Its Effect on Transforming Growth Factor-β1-Induced Extracellular Matrix Expression , 2006, Molecular Pharmacology.

[12]  N. Wahab,et al.  The differential role of Smad2 and Smad3 in the regulation of pro-fibrotic TGFbeta1 responses in human proximal-tubule epithelial cells. , 2006, The Biochemical journal.

[13]  Youhua Liu,et al.  Renal fibrosis: new insights into the pathogenesis and therapeutics. , 2006, Kidney international.

[14]  S. Merajver,et al.  Inhibition of CCN6 (WISP3) expression promotes neoplastic progression and enhances the effects of insulin-like growth factor-1 on breast epithelial cells , 2005, Breast Cancer Research.

[15]  G. Adler,et al.  TGFβ-induced downregulation of E-cadherin-based cell-cell adhesion depends on PI3-kinase and PTEN , 2005, Journal of Cell Science.

[16]  A. Melk,et al.  Epithelial to Mesenchymal Transition During Late Deterioration of Human Kidney Transplants: The Role of Tubular Cells in Fibrogenesis , 2005, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[17]  D. Matsell,et al.  Insulin-like growth factors inhibit podocyte apoptosis through the PI3 kinase pathway. , 2005, Kidney international.

[18]  F. Moreso,et al.  Evaluation of pre-implantation kidney biopsies: comparison of Banff criteria to a morphometric approach. , 2005, Kidney international.

[19]  K. Schlessinger,et al.  GSK-3β sets Snail's pace , 2004, Nature Cell Biology.

[20]  A. Nakao,et al.  Smad3 deficiency attenuates renal fibrosis, inflammation,and apoptosis after unilateral ureteral obstruction. , 2004, Kidney international.

[21]  A. Negri.  Prevention of progressive fibrosis in chronic renal diseases: antifibrotic agents. , 2004, Journal of nephrology.

[22]  H. Werner,et al.  IGF, IGF receptor and overgrowth syndromes. , 2004, Pediatric endocrinology reviews : PER.

[23]  K. Flanders,et al.  Smad3 as a mediator of the fibrotic response , 2004, International journal of experimental pathology.

[24]  K. B. F. Rocha,et al.  The Role of Myofibroblasts and Interstitial Fibrosis in the Progression of Membranous Nephropathy , 2004, Renal failure.

[25]  R. Kalluri,et al.  Epithelial-mesenchymal transition and its implications for fibrosis. , 2003, The Journal of clinical investigation.

[26]  A. Roberts,et al.  Targeted disruption of TGF-beta1/Smad3 signaling protects against renal tubulointerstitial fibrosis induced by unilateral ureteral obstruction. , 2003, The Journal of clinical investigation.

[27]  A. Ivanov,et al.  Endocytosis of epithelial apical junctional proteins by a clathrin-mediated pathway into a unique storage compartment. , 2003, Molecular biology of the cell.

[28]  A. Klippel,et al.  Differential regulation of TGF-β signaling through Smad2, Smad3 and Smad4 , 2003, Oncogene.

[29]  R. Montesano,et al.  Loss of active MEK1-ERK1/2 restores epithelial phenotype and morphogenesis in transdifferentiated MDCK cells. , 2003, American journal of physiology. Cell physiology.

[30]  D. Matsell,et al.  Increased expression of insulin-like growth factors in progressive glomerulonephritis of the MRL lpr mouse , 2003, Lupus.

[31]  R. Kalluri,et al.  BMP-7 counteracts TGF-β1–induced epithelial-to-mesenchymal transition and reverses chronic renal injury , 2003, Nature Medicine.

[32]  Xi He,et al.  A Wnt-Wnt situation. , 2003, Developmental cell.

[33]  E. Neilson,et al.  Evidence that fibroblasts derive from epithelium during tissue fibrosis. , 2002, The Journal of clinical investigation.

[34]  J. Stow,et al.  Protein kinase C regulates endocytosis and recycling of E-cadherin. , 2002, American journal of physiology. Cell physiology.

[35]  M. Rastaldi,et al.  Epithelial-mesenchymal transition of tubular epithelial cells in human renal biopsies. , 2002, Kidney international.

[36]  R. Atkins,et al.  Tubular phenotypic change in progressive tubulointerstitial fibrosis in human glomerulonephritis. , 2001, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[37]  Junwei Yang,et al.  Dissection of key events in tubular epithelial to myofibroblast transition and its implications in renal interstitial fibrosis. , 2001, The American journal of pathology.

[38]  Véronique Delmas,et al.  IGF-II induces rapid β-catenin relocation to the nucleus during epithelium to mesenchyme transition , 2001, Oncogene.

[39]  R. Kucherlapati,et al.  Functional Characterization of Transforming Growth Factor β Signaling in Smad2- and Smad3-deficient Fibroblasts* , 2001, The Journal of Biological Chemistry.

[40]  J. Chapman,et al.  EFFECT OF HISTOLOGICAL DAMAGE ON LONG-TERM KIDNEY TRANSPLANT OUTCOME , 2001, Transplantation.

[41]  V. Han,et al.  Fetal rhesus monkey model of obstructive renal dysplasia. , 2001, Kidney international.

[42]  D. Leroith,et al.  Renal tubulointerstitial injury from ureteral obstruction in the neonatal rat is attenuated by IGF-1. , 2000, Kidney international.

[43]  A. G. de Herreros,et al.  Regulation of E-cadherin/Catenin Association by Tyrosine Phosphorylation* , 1999, The Journal of Biological Chemistry.

[44]  T. Matozaki,et al.  Coendocytosis of cadherin and c-Met coupled to disruption of cell-cell adhesion in MDCK cells – regulation by Rho, Rac and Rab small G proteins , 1999, Oncogene.

[45]  D. Matsell.  Renal dysplasia: new approaches to an old problem. , 1998, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[46]  R. Atkins,et al.  Tubular epithelial-myofibroblast transdifferentiation in progressive tubulointerstitial fibrosis in 5/6 nephrectomized rats. , 1998, Kidney international.

[47]  A. Ridley,et al.  Activation of both MAP kinase and phosphatidylinositide 3-kinase by Ras is required for hepatocyte growth factor/scatter factor-induced adherens junction disassembly. , 1998, Molecular biology of the cell.

[48]  V. Han,et al.  The pathogenesis of multicystic dysplastic kidney disease: insights from the study of fetal kidneys. , 1996, Laboratory investigation; a journal of technical methods and pathology.

[49]  A. Eddy.  Experimental insights into the tubulointerstitial disease accompanying primary glomerular lesions. , 1994, Journal of the American Society of Nephrology : JASN.

[50]  V. Han,et al.  Expression of insulin-like growth factor and binding protein genes during nephrogenesis. , 1994, Kidney international.

[51]  S. Gullans,et al.  An osmotically tolerant inner medullary collecting duct cell line from an SV40 transgenic mouse. , 1993, The American journal of physiology.

[52]  S. Klahr,et al.  Transforming growth factor-beta induces renal epithelial jagged-1 expression in fibrotic disease. , 2002, Journal of the American Society of Nephrology : JASN.

[53]  G. Striker,et al.  Autocrine activation of the IGF-I signaling pathway in mesangial cells isolated from diabetic NOD mice. , 2002, Diabetes.

[54]  E. Dejana,et al.  Regulation of cadherin function by Rho and Rac: modulation by junction maturation and cellular context. , 1999, Molecular biology of the cell.

[55]  V. Han,et al.  Insulin-like growth factor (IGF) and IGF binding protein gene expression in multicystic renal dysplasia. , 1997, Journal of the American Society of Nephrology : JASN.

[56]  C. Brown,et al.  Myofibroblasts and the progression of diabetic nephropathy. , 1997, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[57]  G. Striker,et al.  Glomerulosclerosis: studies of its pathogenesis in humans and animals. , 1994, Contributions to nephrology.

[58]  R. Roeder,et al.  Eukaryotic gene transcription with purified components. , 1983, Methods in enzymology.