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Eddy AA (2000): Molecular basis of renal fibrosis. Pediatr Nephrol 15: 290\u2212301","DOI":"10.1007\/s004670000461"},{"key":"2","unstructured":"2. Bohle A, M\u00fcller GA, Wehrmann M, Mackensen-Haen S & Xiao JC (1996): Pathogenesis of chronic renal failure in the primary glomerulopathies, renal vasculopathies, and chronic interstitial nephritides. Kidney Int Suppl 54: S2\u2212S9"},{"key":"3","doi-asserted-by":"crossref","unstructured":"3. LeBleu VS, Taduri G, O\u2019Connell J, Teng Y, Cooke VG, Woda C, Sugimoto H & Kalluri R (2013): Origin and function of myofibroblasts in kidney fibrosis. Nat Med 19: 1047\u22121053","DOI":"10.1038\/nm.3218"},{"key":"4","doi-asserted-by":"crossref","unstructured":"4. Bucala R, Spiegel LA, Chesney J, Hogan M & Cerami A (1994): Circulating fibrocytes define a new leukocyte subpopulation that mediates tissue repair. Mol Med 1: 71\u221281","DOI":"10.1007\/BF03403533"},{"key":"5","doi-asserted-by":"crossref","unstructured":"5. Niedermeier M, Reich B, Rodriguez Gomez M, Denzel A, Schmidbauer K, G\u00f6bel N, Talke Y, Schweda F & Mack M (2009): CD4+<\/sup> T cells control the differentiation of Gr1+<\/sup> monocytes into fibrocytes. Proc Natl Acad Sci U S A 106: 17892\u221217897","DOI":"10.1073\/pnas.0906070106"},{"key":"6","doi-asserted-by":"crossref","unstructured":"6. Armulik A, Genov\u00e9 G & Betsholtz C (2011): Pericytes: developmental, physiological, and pathological perspectives, problems, and promises. Dev Cell 21: 193\u2212215","DOI":"10.1016\/j.devcel.2011.07.001"},{"key":"7","doi-asserted-by":"crossref","unstructured":"7. Lin SL, Kisseleva T, Brenner DA & Duffield JS (2008): Pericytes and perivascular fibroblasts are the primary source of collagen-producing cells in obstructive fibrosis of the kidney. Am J Pathol 173: 1617\u22121627","DOI":"10.2353\/ajpath.2008.080433"},{"key":"8","doi-asserted-by":"crossref","unstructured":"8. Zeisberg EM, Potenta SE, Sugimoto H, Zeisberg M & Kalluri R (2008): Fibroblasts in kidney fibrosis emerge via endothelial-to-mesenchymal transition. J Am Soc Nephrol 19: 2282\u22122287","DOI":"10.1681\/ASN.2008050513"},{"key":"9","doi-asserted-by":"crossref","unstructured":"9. Holian J, Qi W, Kelly DJ, Zhang Y, Mreich E, Pollock CA & Chen XM (2008): Role of Kruppel-like factor 6 in transforming growth factor-\u03b2<\/i>1-induced epithelial-mesenchymal transition of proximal tubule cells. Am J Physiol Renal Physiol 295: F1388\u2212F1396","DOI":"10.1152\/ajprenal.00055.2008"},{"key":"10","doi-asserted-by":"crossref","unstructured":"10. Lan HY (2003): Tubular epithelial-myofibroblast transdifferentiation mechanisms in proximal tubule cells. Curr Opin Nephrol Hypertens 12: 25\u221229","DOI":"10.1097\/00041552-200301000-00005"},{"key":"11","doi-asserted-by":"crossref","unstructured":"11. Shimizu M, Kondo S, Urushihara M, Takamatsu M, Kanemoto K, Nagata M & Kagami S (2006): Role of integrin-linked kinase in epithelial-mesenchymal transition in crescent formation of experimental glomerulonephritis. Nephrol Dial Transplant 21: 2380\u22122390","DOI":"10.1093\/ndt\/gfl243"},{"key":"12","doi-asserted-by":"crossref","unstructured":"12. Bedi S, Vidyasagar A & Djamali A (2008): Epithelial-to-mesenchymal transition and chronic allograft tubulointerstitial fibrosis. Transplant Rev (Orlando) 22: 1\u22125","DOI":"10.1016\/j.trre.2007.09.004"},{"key":"13","doi-asserted-by":"crossref","unstructured":"13. Liu Y (2004): Epithelial to mesenchymal transition in renal fibrogenesis: pathologic significance, molecular mechanism, and therapeutic intervention. J Am Soc Nephrol 15: 1\u221212","DOI":"10.1097\/01.ASN.0000106015.29070.E7"},{"key":"14","doi-asserted-by":"crossref","unstructured":"14. Li Y, Kang YS, Dai C, Kiss LP, Wen X & Liu Y (2008): Epithelial-to-mesenchymal transition is a potential pathway leading to podocyte dysfunction and proteinuria. Am J Pathol 172: 299\u2212308","DOI":"10.2353\/ajpath.2008.070057"},{"key":"15","doi-asserted-by":"crossref","unstructured":"15. Li Y, Dai C, Wu C & Liu Y (2007): PINCH-1 promotes tubular epithelial-to-mesenchymal transition by interacting with integrin-linked kinase. J Am Soc Nephrol 18: 2534\u22122543","DOI":"10.1681\/ASN.2007030315"},{"key":"16","doi-asserted-by":"crossref","unstructured":"16. Phanish MK, Wahab NA, Colville-Nash P, Hendry BM & Dockrell ME (2006): The differential role of Smad2 and Smad3 in the regulation of pro-fibrotic TGFbeta1 responses in human proximal-tubule epithelial cells. Biochem J 393: 601\u2212607","DOI":"10.1042\/BJ20051106"},{"key":"17","doi-asserted-by":"crossref","unstructured":"17. Thornton TM, Pedraza-Alva G, Deng B et<\/i> al<\/i> (2008): Phosphorylation by p38 MAPK as an alternative pathway for GSK3\u03b2<\/i> inactivation. Science 320: 667\u2212670","DOI":"10.1126\/science.1156037"},{"key":"18","doi-asserted-by":"crossref","unstructured":"18. Nusse R (2005): Wnt signaling in disease and in development. Cell Res 15: 28\u221232","DOI":"10.1038\/sj.cr.7290260"},{"key":"19","doi-asserted-by":"crossref","unstructured":"19. Moon RT, Kohn AD, De Ferrari GV & Kaykas A (2004): WNT and beta-catenin signaling: diseases and therapies. Nat Rev Genet 5: 691\u2212701","DOI":"10.1038\/nrg1427"},{"key":"20","doi-asserted-by":"crossref","unstructured":"20. Kohn AD & Moon RT (2005): Wnt and calcium signaling: beta-catenin-independent pathways. Cell Calcium 38: 439\u2212446","DOI":"10.1016\/j.ceca.2005.06.022"},{"key":"21","doi-asserted-by":"crossref","unstructured":"21. Wynn TA & Ramalingam TR (2012): Mechanisms of fibrosis: therapeutic translation for fibrotic disease. Nat Med 18: 1028\u22121040","DOI":"10.1038\/nm.2807"},{"key":"22","doi-asserted-by":"crossref","unstructured":"22. Yasuniwa Y, Izumi H, Wang KY et<\/i> al<\/i> (2010): Circadian disruption accelerates tumor growth and angio\/stromagenesis through a Wnt signaling pathway. PLoS ONE 5: e15330","DOI":"10.1371\/journal.pone.0015330"},{"key":"23","doi-asserted-by":"crossref","unstructured":"23. He W, Dai C, Li Y, Zeng G, Monga SP & Liu Y (2009): Wnt \/\u03b2<\/i>-catenin signaling promotes renal interstitial fibrosis. J Am Soc Nephrol 20: 765\u2212776","DOI":"10.1681\/ASN.2008060566"},{"key":"24","doi-asserted-by":"crossref","unstructured":"24. Kuma A, Yamada S, Wang KY, Kitamura N, Yamaguchi T, Iwai Y, Izumi H, Tamura M, Otsuji Y & Kohno K (2014): Role of WNT10A-expressing kidney fibroblasts in acute interstitial nephritis. PLoS ONE 9: e103240","DOI":"10.1371\/journal.pone.0103240"},{"key":"25","doi-asserted-by":"crossref","unstructured":"25. Yamagata K, Li X, Ikegaki S, Oneyama C, Okada M, Nishita M & Minami Y (2012): Dissection of Wnt5a-Ror2 signaling leading to matrix metalloproteinase (MMP-13) expression. J Biol Chem 287: 1588\u22121599","DOI":"10.1074\/jbc.M111.315127"},{"key":"26","doi-asserted-by":"crossref","unstructured":"26. Li X, Yamagata K, Nishita M, Endo M, Arfian N, Rikitake Y, Emoto N, Hirata K, Tanaka Y & Minami Y (2013): Activation of Wnt5a-Ror2 signaling associated with epithelial-to-mesenchymal transition of tubular epithelial cells during renal fibrosis. Genes Cells 18: 608\u2212619","DOI":"10.1111\/gtc.12064"},{"key":"27","doi-asserted-by":"crossref","unstructured":"27. Huber MA, Kraut N & Beug H (2005): Molecular requirements for epithelial-mesenchymal transition during tumor progression. Curr Opin Cell Biol 17: 548\u2212558","DOI":"10.1016\/j.ceb.2005.08.001"},{"key":"28","doi-asserted-by":"crossref","unstructured":"28. Tsubakihara Y, Gejyo F, Nishi S, Iino Y, Watanabe Y, Suzuki M, Saito A, Akiba T, Hirakata H & Akizawa T (2012): High target hemoglobin with erythropoiesis-stimulating agents has advantages in the renal function of non-dialysis chronic kidney disease patients. Ther Apher Dial 16: 529\u2212540","DOI":"10.1111\/j.1744-9987.2012.01082.x"},{"key":"29","doi-asserted-by":"crossref","unstructured":"29. Palmer SC, Navaneethan SD, Crig JC et<\/i> al<\/i> (2010): Meta-analysis: erythropoiesis-stimulating agents in patients with chronic kidney disease. Ann Intern Med 153: 23\u221233","DOI":"10.7326\/0003-4819-153-1-201007060-00252"},{"key":"30","doi-asserted-by":"crossref","unstructured":"30. Pfeffer MA, Burdmann EA, Chen CY et<\/i> al<\/i> (2009): A trial of darbepoetin alfa in type 2 diabetes and chronic kidney disease. N Engl J Med 361: 2019\u22122032","DOI":"10.1056\/NEJMoa0907845"},{"key":"31","doi-asserted-by":"crossref","unstructured":"31. Asada N, Takase M, Nakamura J et<\/i> al<\/i> (2011): Dysfunction of fibroblasts of extrarenal origin underlies renal fibrosis and renal anemia in mice. J Clin Invest 121: 3981\u22123990","DOI":"10.1172\/JCI57301"},{"key":"32","doi-asserted-by":"crossref","unstructured":"32. Bernhardt WM, Wiesener MS, Scigalla P, Chou J, Schmieder RE, G\u00fcnzler V & Eckardt KU (2010): Inhibition of prolyl hydroxylases increases erythropoietin production in ESRD. J Am Soc Nephrol 21: 2151\u22122156","DOI":"10.1681\/ASN.2010010116"},{"key":"33","doi-asserted-by":"crossref","unstructured":"33. Vanholder R, De Smet R, Glorieux G et<\/i> al<\/i> (2003): Review on uremic toxins: classification, concentration, and interindividual variability. Kidney Int 63: 1934\u22121943","DOI":"10.1046\/j.1523-1755.2003.00924.x"},{"key":"34","unstructured":"34. Miyazaki T, Ise M, Hirata M, Endo K, Ito Y, Seo H & Niwa T (1997): Indoxyl sulfate stimulates renal synthesis of transforming growth factor-beta 1 and progression of renal failure. Kidney Int Suppl 63: S211\u2212S214"},{"key":"35","doi-asserted-by":"crossref","unstructured":"35. Motojima M, Hosokawa A, Yamato H, Muraki T & Yoshioka T (2003): Uremic toxins of organic anions up-regulate PAI-1 expression by induction of NF-\u03baB and free radical in proximal tubular cells. Kidney Int 63: 1671\u22121680","DOI":"10.1046\/j.1523-1755.2003.00906.x"},{"key":"36","doi-asserted-by":"crossref","unstructured":"36. Kawakami T, Inagi R, Wada T, Tanaka T, Fujita T & Nangaku M (2010): Indoxyl sulfate inhibits proliferation of human proximal tubular cells via endoplasmic reticulum stress. Am J Physiol Renal Physiol 299: F568\u2212F576","DOI":"10.1152\/ajprenal.00659.2009"},{"key":"37","doi-asserted-by":"crossref","unstructured":"37. 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Fan JM, Huang XR, Ng YY, Nikolic-Paterson DJ, Mu W, Atkins RC & Lan HY (2001): Interleukin-1 induces tubular epithelial-myofibroblast transdifferentiation through a transforming growth factor-beta1-dependent mechanism in vitro. Am J Kidney Dis 37: 820\u2212831","DOI":"10.1016\/S0272-6386(01)80132-3"},{"key":"41","doi-asserted-by":"crossref","unstructured":"41. Kitani A, Fuss I, Nakamura K, Kumaki F, Usui T & Strober W (2003): Transforming growth factor (TGF)-beta1-producing regulatory T cells induce Smad-mediated interleukin 10 secretion that facilitates coordinated immunoregulatory activity and amelioration of TGF-beta1-mediated fibrosis. J Exp Med 198: 1179\u22121188","DOI":"10.1084\/jem.20030917"},{"key":"42","doi-asserted-by":"crossref","unstructured":"42. Richeldi L & du Bois RM (2011): Pirfenidone in idiopathic pulmonary fibrosis: the CAPACITY program. Expert Rev Respir Med 5: 473\u2212481","DOI":"10.1586\/ers.11.52"},{"key":"43","doi-asserted-by":"crossref","unstructured":"43. 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