The Role of Tubular Epithelial-Mesenchymal Transition in Progressive Kidney Disease

Cells Tissues Organs - Tập 185 Số 1-3 - Trang 222-231 - 2007
Wendy C. Burns1, Phillip Kantharidis2, Merlin C. Thomas2
1Danielle Alberti Memorial Centre for Diabetes Complications, Baker Medical Research Institute, Melbourne, Australia. wendy.burns@baker.edu.au
2Baker Heart & Diabetes Institute;

Tóm tắt

The accumulation of interstitial matrix represents the final common pathway of most forms of kidney disease. Much of this matrix is synthesized by interstitial myofibroblasts, recruited from resident fibroblasts and circulating precursors. In addition, a significant proportion is derived from epithelial-mesenchymal transition (EMT) of tubuloepithelial cells. The importance of EMT has been demonstrated in experimental models, where blockade of EMT attenuates renal fibrosis. Although a number of factors may initiate EMT in the kidney, the most potent is transforming growth factor-β1 (TGF-β1). Moreover, many other prosclerotic factors have effects on EMT indirectly, via induction of TGF-β1. Signaling events in this pathway include activation of Smad/integrin-linked kinase (ILK) and connective tissue growth factor (CTGF). Basement membrane integrity is also a key regulator of EMT. In particular, overexpression of matrix metalloproteinase-2 has a key role in the initiation of EMT, membrane dissolution, and the interstitial transit of transformed mesenchymal cells. Endogenous inhibitors of EMT also play an important counterregulatory role both to prevent EMT and stimulate uncommitted cells to regain their tubular phenotype (mesenchymal-epithelial transition). Such inhibitors represent a potential therapeutic approach, offering a mechanism to slow or even redress established renal fibrosis.

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Tài liệu tham khảo

10.1111%2Fj.1523-1755.2005.00486.x

10.1097%2F01.ASN.0000033611.79556.AE

10.1677%2Fjoe.0.1780169

10.1681%2FASN.2006050525

10.1097%2F01.ASN.0000032522.29672.0A

10.1016%2FS0002-9440%2810%2964327-1

10.1096%2Ffj.06-5898fje

10.1111%2Fj.1523-1755.2005.00555.x

10.2337%2Fdiabetes.53.4.1119

10.1097%2F01.ASN.0000139479.09658.EE

10.1016%2FS0272-6386%2801%2980132-3

10.1046%2Fj.1523-1755.1999.00656.x

10.2337%2Fdiacare.26.9.2632

10.1159%2F000020635

10.1097%2F01.ASN.0000077411.98742.54

10.1016%2F0272-6386%2895%2990610-X

10.1046%2Fj.1523-1755.2003.00306.x

10.1074%2Fjbc.M305019200

10.1242%2Fjcs.00389

10.1172%2FJCI200215518

10.1242%2Fjcs.02465

10.1172%2FJCI200320530

10.1097%2F00041552-200301000-00005

10.1097%2F01.ASN.0000067632.04658.B8

10.1002%2Fjcb.20380

10.1083%2Fjcb.200601018

10.1096%2Ffj.04-2273com

10.1097%2F01.ASN.0000014252.37680.E4

10.1172%2FJCI200317913

10.1097%2F01.ASN.0000106015.29070.E7

10.1074%2Fjbc.M503304200

10.1093%2Fndt%2F15.suppl_6.74

10.1681%2FASN.2004060436

10.1038%2F35043051

10.1093%2Femboj%2F19.8.1745

10.1093%2Fndt%2Fgfh967

10.1074%2Fjbc.M210433200

10.1002%2F%28SICI%291097-4652%28199910%29181%3A1%3C153%3A%3AAID-JCP16%3E3.0.CO%3B2-K

10.1681%2FASN.2004040339

10.1172%2FJCI200111951

10.1681%2FASN.2004110943

10.1074%2Fjbc.M211304200

10.1042%2FBJ20051106

10.1097%2F01.bor.0000139310.77347.9c

10.1152%2Fajprenal.00179.2004

10.1046%2Fj.1523-1755.2002.00430.x

10.1152%2Fajpcell.00306.2005

10.1172%2FJCI200319270

10.1172%2FJCI200112367

10.2337%2Fdiabetes.40.10.1328

10.1046%2Fj.1523-1755.2002.00333.x

10.1016%2FS0968-0004%2899%2901519-4

10.1053%2Fj.ackd.2005.01.008

10.1681%2FASN.2005010013

10.1210%2Fen.2002-220619

10.1210%2Fen.142.5.1760

10.1007%2Fs00125-004-1423-6

10.1091%2Fmbc.E04-08-0658

10.1093%2Fndt%2Fgfh570

10.1046%2Fj.1523-1755.2003.00035.x

10.1016%2FS0002-9440%2810%2963909-0

10.1681%2FASN.2003090795

10.1016%2FS0002-9440%2810%2962533-3

10.1038%2Fnm888

10.1074%2Fjbc.M413102200

10.1016%2FS0378-1119%2800%2900162-1

10.1097%2F01.ASN.0000093460.24823.5B