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ЭПИТЕЛИАЛЬНО-МЕЗЕНХИМАЛЬНАЯ ТРАНСФОРМАЦИЯ КАК БИОМАРКЕР ПОЧЕЧНОГО ФИБРОЗА: ГОТОВЫ ЛИ МЫ ПРИМЕНИТЬ ТЕОРЕТИЧЕСКИЕ ЗНАНИЯ НА ПРАКТИКЕ?

https://doi.org/10.24884/1561-6274-2013-17-4-9-16

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Аннотация

За последние 20 лет концепция эпителиально-мезенхимальной трансформации (ЭМТ), которая ранее была ограничена рамками эмбриологии и онкологии, была применена к фиброзу и, в частности, к почечному фиброзу. Интерес к ЭМТ в контексте почечного фиброза проистекает из наблюдений, показавших, что эпителиальные клетки могут претерпевать фенотипические изменения, делающие их похожими на фибробласты. Гипотеза о том, что ЭМТ является источником интерстициальных фибробластов, стала предметом ожесточенных дебатов, что, в свою очередь, привело к недооценке ЭМТ как биомаркера почечного фиброза. В этом обзоре мы описываем эволюцию методов распознавания ЭМТ при заболеваниях почек, протекающих с формированием фиброза, и коснёмся клинического значения этих методов в диагностике различных заболеваний почек. Ввиду большого разнообразия этих методик и необходимости их стандартизации, мы предостерегаем от некорректного использования маркеров ЭМТ. Мы предлагаем совместное использование β-катенина и виментина для диагностики ЭМТ в нефрологии, поскольку этот метод одновременно является чувствительным, и имеет прогностическое значение, что удовлетворяет критериям скринингового теста. И наконец, мы обсуждаем потенциальный интерес диагностики ЭМТ для понимания механизмов почечного фиброза и клинической практики в целом.

Об авторах

П. Галишон
Institut national de la santé et de la recherchemédicale (INSERM); Université Pierre et Marie Curie, Sorbonne Universités; Urgences néphrologiques et transplantation rénale de l’hôpitalTenon, assistance publique des hôpitaux de Paris
Франция

UMR S702, 4 rue de la Chine, Paris, 75020

4 placeJussieu, Paris, 75005

4 rue de la Chine, Paris, 75020



А. Гертиг
Institut national de la santé et de la recherchemédicale (INSERM); Université Pierre et Marie Curie, Sorbonne Universités; Urgences néphrologiques et transplantation rénale de l’hôpitalTenon, assistance publique des hôpitaux de Paris
Франция

UMR S702, 4 rue de la Chine, Paris, 75020

4 placeJussieu, Paris, 75005

4 rue de la Chine, Paris, 75020



И. И. Трофименко

Россия

Перевод



Список литературы

1. Hay ED. The mesenchymal cell, its role in the embryo, and the remarkable signaling mechanisms that create it. Developmental Dynamics 2005; 233:706-720

2. Kalluri R, Weinberg RA. The basics of epithelial-mesenchymal transition. J Clin Invest 2009; 119:1420-1428

3. Thiery JP, Acloque H, Huang RY, Nieto MA. Epithelialmesenchymal transitions in development and disease. Cell 2009; 139:871-890

4. Strutz F, Okada H, Lo CW, Danoff T, Carone RL, Tomaszewski JE, Neilson EG. Identification and characterization of a fibroblast marker: FSP1. J Cell Biol 1995; 130:393-405

5. Iwano M, Plieth D, Danoff TM, Xue C, Okada H, Neilson EG. Evidence that fibroblasts derive from epithelium during tissue fibrosis. J Clin Invest 2002; 110:341-350

6. Zeisberg M, Hanai J, Sugimoto H, Mammoto T, Charytan D, Strutz F, Kalluri R. BMP-7 counteracts TGF-beta1-induced epithelial-to-mesenchymal transition and reverses chronic renal injury. Nat Med 2003; 9:964-968

7. Faulkner JL, Szcykalski LM, Springer F, Barnes JL. Origin of interstitial fibroblasts in an accelerated model of angiotensin II-induced renal fibrosis. Am J Pathol 2005; 167:1193-1205

8. Humphreys BD, Lin SL, Kobayashi A, Hudson TE, Nowlin BT, Bonventre JV, Valerius MT, McMahon AP, Duffield JS. Fate tracing reveals the pericyte and not epithelial origin of myofibroblasts in kidney fibrosis. Am J Pathol 2010; 176:85-97

9. Zeisberg M, Duffield JS. Resolved: EMT produces fibroblasts in the kidney. J Am Soc Nephrol 2010; 21:1247-1253

10. Ross MH, Romrell LJ, Kaye GI. Histology. A text and atlas 1995

11. Hertig A, Flier SN, Kalluri R. Contribution of epithelial plasticity to renal transplantation-associated fibrosis. Transplant Proc 2010; 42:S7-12

12. Essawy M, Soylemezoglu O, Muchaneta-Kubara EC, Shortland J, Brown CB, elNahas AM. Myofibroblasts and the progression of diabetic nephropathy. Nephrol Dial Transplant 1997; 12:43-50

13. Giannico G, Yang H, Neilson EG, Fogo AB. Dystroglycan in the diagnosis of FSGS. Clin J Am Soc Nephrol 2009; 4:1747-1753

14. Nishitani Y, Iwano M, Yamaguchi Y, Harada K, Nakatani K, Akai Y, Nishino T, Shiiki H, Kanauchi M, Saito Y, Neilson EG. Fibroblast-specific protein 1 is a specific prognostic marker for renal survival in patients with IgAN. Kidney Int 2005; 68:1078-1085

15. Scherer A, Gwinner W, Mengel M, Kirsch T, Raulf F, Szustakowski JD, Hartmann N, Staedtler F, Engel G, Klupp J, et al. Transcriptome changes in renal allograft protocol biopsies at 3 months precede the onset of interstitial fibrosis/tubular atrophy (IF/TA) at 6 months. Nephrol Dial Transplant 2009; 24:2567-2575

16. Rodder S, Scherer A, Raulf F, Berthier CC, Hertig A, Couzi L, Durrbach A, Rondeau E, Marti HP. Renal allografts with IF/TA display distinct expression profiles of metzincins and related genes. Am J Transplant 2009; 9:517-526

17. Einecke G, Reeve J, Sis B, Mengel M, Hidalgo L, Famulski KS, Matas A, Kasiske B, Kaplan B, Halloran PF. A molecular classifier for predicting future graft loss in late kidney transplant biopsies. J Clin Invest 2010; 120:1862-1872

18. Muthukumar T, Ding R, Snopkowski C, Hummel A, Sharma VK, Dadhania D, Seshan S, Suthanthiran M, Anglicheau D. Noninvasive diagnosis of renal interstitial fibrosis and tubular atrophy (IF/TA) by measurement of epithelial to mesenchymal transition (EMT) genes in urine. American Journal of Transplantation 2009; 9:226-227

19. Le Hir M, Hegyi I, Cueni-Loffing D, Loffing J, Kaissling B. Characterization of renal interstitial fibroblast-specific protein 1/S100A4-positive cells in healthy and inflamed rodent kidneys. Histochem Cell Biol 2005; 123:335-346.

20. Okada H, Ban S, Nagao S, Takahashi H, Suzuki H, Neilson EG. Progressive renal fibrosis in murine polycystic kidney disease: an immunohistochemical observation. Kidney Int 2000; 58:587-597

21. Osterreicher CH, Penz-Osterreicher M, Grivennikov SI, Guma M, Koltsova EK, Datz C, Sasik R, Hardiman G, Karin M, Brenner DA. Fibroblast-specific protein 1 identifies an inflammatory subpopulation of macrophages in the liver. Proc Natl Acad Sci USA 2011; 108:308-313

22. Gibbs FE, Barraclough R, Platt-Higgins A, Rudland PS, Wilkinson MC, Parry EW. Immunocytochemical distribution of the calcium-binding protein p9Ka in normal rat tissues: variation in the cellular location in different tissues. J Histochem Cytochem 1995; 43:169-180

23. Inoue T, Plieth D, Venkov CD, Xu C, Neilson EG. Antibodies against macrophages that overlap in specificity with fibroblasts. Kidney Int 2005; 67:2488-2493

24. Flatmark K, Maelandsmo GM, Mikalsen SO, Nustad K, Varaas T, Rasmussen H, Meling GI, Fodstad O, Paus E. Immunofluorometric assay for the metastasis-related protein S100A4: release of S100A4 from normal blood cells prohibits the use of S100A4 as a tumor marker in plasma and serum. Tumour Biol 2004; 25:31-40

25. Grigorian M, Tulchinsky E, Burrone O, Tarabykina S, Georgiev G, Lukanidin E. Modulation of mts1 expression in mouse and human normal and tumor cells. Electrophoresis 1994;15:463-468

26. Cabezon T, Celis JE, Skibshoj I, Klingelhofer J, Grigorian M, Gromov P, Rank F, Myklebust JH, Maelandsmo GM, Lukanidin E, Ambartsumian N. Expression of S100A4 by a variety of cell types present in the tumor microenvironment of human breast cancer. Int J Cancer 2007; 121:1433-1444

27. Okada H, Danoff TM, Kalluri R, Neilson EG. Early role of Fsp1 in epithelialmesenchymal transformation. Am J Physiol 1997; 273:F563-574

28. Schneider M, Hansen JL, Sheikh SP. S100A4: a common mediator of epithelial-mesenchymal transition, fibrosis and regeneration in diseases? J Mol Med 2008; 86:507-522

29. Boye K, Maelandsmo GM. S100A4 and metastasis: a small actor playing many roles. Am J Pathol 2010; 176:528-535

30. Hertig A, Verine J, Mougenot B, Jouanneau C, Ouali N, Sebe P, Glotz D, Ancel PY, Rondeau E, Xu-Dubois YC. Risk factors for early epithelial to mesenchymal transition in renal grafts. Am J Transplant 2006; 6:2937-2946

31. Zeisberg M, Neilson EG. Biomarkers for epithelial-mesenchymal transitions. J Clinical Investigation 2009; 119:1429-1437

32. Prozialeck WC, Lamar PC, Appelt DM. Differential expression of E-cadherin, N-cadherin and beta-catenin in proximal and distal segments of the rat nephron. BMC Physiol 2004; 4:10

33. Robertson D, Savage K, Reis-Filho JS, Isacke CM. Multiple immunofluorescence labelling of formalin-fixed paraffinembedded (FFPE) tissue. BMC Cell Biol 2008; 9:13

34. Mendez MG, Kojima S, Goldman RD. Vimentin induces changes in cell shape, motility, and adhesion during the epithelial to mesenchymal transition. Faseb J 2010; 24:1838-1851

35. Zhu QS, Rosenblatt K, Huang KL, Lahat G, Brobey R, Bolshakov S, Nguyen T, Ding Z, Belousov R, Bill K, et al. Vimentin is a novel AKT1 target mediating motility and invasion. Oncogene 2011; 30:457-470

36. Lahat G, Zhu QS, Huang KL, Wang S, Bolshakov S, Liu J, Torres K, Langley RR, Lazar AJ, Hung MC, Lev D. Vimentin is a novel anti-cancer therapeutic target; insights from in vitro and in vivo mice xenograft studies. PLoS One 2010; 5:e10105

37. Wei J, Xu G, Wu M, Zhang Y, Li Q, Liu P, Zhu T, Song A, Zhao L, Han Z, et al. Overexpression of vimentin contributes to prostate cancer invasion and metastasis via src regulation. Anticancer Res 2008; 28:327-334

38. Eckes B, Colucci-Guyon E, Smola H, Nodder S, Babinet C, Krieg T, Martin P. Impaired wound healing in embryonic and adult mice lacking vimentin. J Cell Sci 2000; 113(Pt 13):2455-2462

39. Terzi F, Henrion D, Colucci-Guyon E, Federici P, Babinet C, Levy BI, Briand P, Friedlander G. Reduction of renal mass is lethal in mice lacking vimentin. Role of endothelin-nitric oxide imbalance. J Clin Invest 1997; 100:1520-1528

40. Terzi F, Maunoury R, Colucci-Guyon E, Babinet C, Federici P, Briand P, Friedlander G. Normal tubular regeneration and differentiation of the post-ischemic kidney in mice lacking vimentin. Am J Pathol 1997; 150:1361-1371

41. Maretta M, Marettova E. Immunohistochemical demonstration of vimentin and S-100 protein in the kidneys. Gen Physiol Biophys1999; 18(1):100-102

42. Holthofer H, Miettinen A, Lehto VP, Lehtonen E, Virtanen I. Expression of vimentin and cytokeratin types of intermediate filament proteins in developing and adult human kidneys. Lab Invest 1984; 50:552-559

43. Grone HJ, Weber K, Grone E, Helmchen U, Osborn M. Coexpression of keratin and vimentin in damaged and regenerating tubular epithelia of the kidney. Am J Pathol 1987; 129:1-8

44. Witzgall R, Brown D, Schwarz C, Bonventre JV. Localization of proliferating cell nuclear antigen, vimentin, c-Fos, and clusterin in the postischemic kidney. Evidence for a heterogenous genetic response among nephron segments, and a large pool of mitotically active and dedifferentiated cells. J Clin Invest 1994; 93:2175-2188

45. Jinde K, Nikolic-Paterson DJ, Huang XR, Sakai H, Kurokawa K, Atkins RC, Lan HY. Tubular phenotypic change in progressive tubulointerstitial fibrosis in human glomerulonephritis. Am J Kidney Dis 2001; 38:761-769

46. Rastaldi MP, Ferrario F, Giardino L, Dell’Antonio G, Grillo C, Grillo P, Strutz F, Muller GA, Colasanti G, D’Amico G. Epithelialmesenchymal transition of tubular epithelial cells in human renal biopsies. Kidney Int 2002; 62:137-146

47. Vongwiwatana A, Tasanarong A, Rayner DC, Melk A, Halloran PF: Epithelial tomesenchymal transition during late deterioration of human kidney transplants: the role of tubular cells in fibrogenesis. Am J Transplant 2005; 5:1367-1374

48. He W, Dai C, Li Y, Zeng G, Monga SP, Liu Y. Wnt/beta-catenin signaling promotes renal interstitial fibrosis. J Am Soc Nephrol 2009; 20:765-776

49. He W, Kang YS, Dai C, Liu Y. Blockade of Wnt/{beta}- Catenin signaling by paricalcitol ameliorates proteinuria and kidney injury. J Am SocNephrol 2011; 22:90-103

50. Surendran K, Schiavi S, Hruska KA. Wnt-dependent betacatenin signaling is activated after unilateral ureteral obstruction, and recombinant secreted frizzled-related protein 4 alters the progression of renal fibrosis. J Am Soc Nephrol 2005; 16:2373-2384

51. vonToerne C, Schmidt C, Adams J, Kiss E, Bedke J, Porubsky S, Gretz N, Lindenmeyer MT, Cohen CD, Grone HJ, Nelson PJ. Wnt pathway regulation in chronic renal allograft damage. Am J Transplant 2009; 9:2223-2239

52. Hertig A, Bonnard G, Ulinski T, Colombat M, Jouanneau C, Baugey E, Bensman A, Ronco P, Rondeau E, Xu-Dubois Y-C. Tubular nuclear accumulation of snail and epithelial phenotypic changes in human myeloma cast nephropathy. Human Pathology 2011

53. Brenner BM. The Kidney 2008; 1: 995-996

54. Yamaguchi Y, Iwano M, Suzuki D, Nakatani K, Kimura K, Harada K, Kubo A, Akai Y, Toyoda M, Kanauchi M, et al. Epithelialmesenchymal transition as a potential explanation for podocyte depletion in diabetic nephropathy. Am J Kidney Dis 2009; 54:653-664

55. Solez K, Colvin RB, Racusen LC, Haas M, Sis B, Mengel M, Halloran PF, Baldwin W, Banfi G, Collins AB, et al. Banff 07 classification of renal allograft pathology: updates and future directions. Am J Transplant 2008; 8:753-760

56. Vitalone MJ, O’Connell PJ, Jimenez-Vera E, Yuksel A, Wavamunno M, Fung CL, Chapman JR, Nankivell BJ. Epithelialto-mesenchymal transition in early transplant tubulointerstitial damage. J Am Soc Nephrol 2008; 19:1571-1583

57. Hertig A, Anglicheau D, Verine J, Pallet N, Touzot M, Ancel PY, Mesnard L, Brousse N, Baugey E, Glotz D, et al. Early Epithelial phenotypic changes predict graft fibrosis. J Am Soc Nephrol 2008

58. de Matos AC, Camara NO, Tonato EJ, Durao Junior Mde S, Franco MF, Moura LA, Pacheco-Silva A. Vimentin expression and myofibroblast infiltration are early markers of renal dysfunction in kidney transplantation: an early stage of chronic allograft dysfunction? Transplant Proc 2010; 42:3482-3488

59. Kalluri R, Neilson EG: Epithelial-mesenchymal transition and its implications for fibrosis. J Clin Invest 2003; 112:1776-1784

60. Liu Y. New insights into epithelial-mesenchymal transition in kidney fibrosis. J Am Soc Nephrol 2010; 21:212-222

61. Thiery JP, Sleeman JP. Complex networks orchestrate epithelial-mesenchymal transitions. Nat Rev Mol Cell Biol 2006; 7:131-142

62. Peinado H, Del Carmen Iglesias-de la Cruz M, Olmeda D, Csiszar K, Fong KS, Vega S, Nieto MA, Cano A, Portillo F. A molecular role for lysyl oxidase-like 2 enzyme in snail regulation and tumor progression. Embo J 2005; 24:3446-3458

63. Higgins DF, Kimura K, Bernhardt WM, Shrimanker N, Akai Y, Hohenstein B, Saito Y, Johnson RS, Kretzler M, Cohen CD, et al: Hypoxia promotes fibrogenesis in vivo via HIF-1 stimulation of epithelial-to-mesenchymal transition. J Clin Invest 2007;117:3810- 3820

64. Sun S, Ning X, Zhang Y, Lu Y, Nie Y, Han S, Liu L, Du R, Xia L, He L, Fan D. Hypoxia-inducible factor-1alpha induces Twist expression in tubular epithelial cells subjected to hypoxia, leading to epithelial-to-mesenchymal transition. Kidney Int 2009; 75:1278-1287

65. Yang J, Liu Y. Blockage of tubular epithelial to myofibroblast transition by hepatocyte growth factor prevents renal interstitial fibrosis. J Am Soc Nephrol 2002; 13:96-107

66. Reese S, Vidyasagar A, Jacobson L, Acun Z, Esnault S, Hullett D, Malter JS, Djamali A. The Pin 1 inhibitor juglone attenuates kidney fibrogenesis via Pin 1-independent mechanisms in the unilateral ureteral occlusion model. Fibrogenesis Tissue Repair 2010; 3:1

67. Hills CE, Squires PE. TGF-beta1-induced epithelial-tomesenchymal transition and therapeutic intervention in diabetic nephropathy. Am J Nephrol 2009; 31:68-74

68. Bedi S, Vidyasagar A, Djamali A. Epithelial-to-mesenchymal transition and chronic allograft tubulointerstitial fibrosis. Transplant Rev (Orlando) 2008; 22:1-5


Для цитирования:


Галишон П., Гертиг А., Трофименко И.И. ЭПИТЕЛИАЛЬНО-МЕЗЕНХИМАЛЬНАЯ ТРАНСФОРМАЦИЯ КАК БИОМАРКЕР ПОЧЕЧНОГО ФИБРОЗА: ГОТОВЫ ЛИ МЫ ПРИМЕНИТЬ ТЕОРЕТИЧЕСКИЕ ЗНАНИЯ НА ПРАКТИКЕ? Нефрология. 2013;17(4):9-16. https://doi.org/10.24884/1561-6274-2013-17-4-9-16

For citation:


Galichon P., Hertig A., Trofimenko I.I. EPITHELIAL TO MESENCHYMAL TRANSITION AS A BIOMARKER IN RENAL FIBROSIS: ARE WE READY FOR THE BEDSIDE? Nephrology (Saint-Petersburg). 2013;17(4):9-16. (In Russ.) https://doi.org/10.24884/1561-6274-2013-17-4-9-16

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ISSN 1561-6274 (Print)
ISSN 2541-9439 (Online)