Beneficial Effects of the Rho Kinase Inhibitor Y27632 in Murine Puromycin Aminonucleoside Nephrosis

Kidney and Blood Pressure Research - Tập 31 Số 2 - Trang 111-121 - 2008
Liming Wang1, Mathew J. Ellis1, Timothy A. Fields2, David N. Howell2, Robert F. Spurney1
1Division of Nephrology, Department of Medicine, and
2Department of Pathology, Duke University and Durham VA Medical Centers, Durham, N.C. , USA

Tóm tắt

<i>Background and Aims:</i> Rho kinase (ROCK) inhibition reduces systemic blood pressure (BP) and decreases renal damage in animal models of kidney disease. The aim of this study was to determine if ROCK inhibition might have beneficial effects in glomerular disease processes that are independent of systemic BP. <i>Methods:</i> We investigated the effects of the ROCK inhibitor Y27632 and hydralazine in murine puromycin aminonucleoside (PAN) nephrosis. <i>Results:</i> Treatment with either Y27632 or hydralazine similarly reduced systolic BP compared to vehicle-treated controls. Seven days after treatment with PAN, albuminuria, proteinuria and effacement of podocyte foot processes were significantly reduced in Y27632- and hydralazine-treated mice compared to vehicle-treated animals. Treatment with PAN significantly reduced expression of the podocyte proteins nephrin and Neph1, and the loss of glomerular nephrin was attenuated by treatment with Y27632 but not by treatment with hydralazine. In cultured podocytes, PAN potently activated both Rho and ROCK, and PAN-induced ROCK activation was prevented by Y27632. <i>Conclusions:</i> The ROCK inhibitor Y27632 attenuated glomerular nephrin loss in murine PAN nephrosis independent of its effects on systemic BP.

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Tài liệu tham khảo

10.1097%2F01.ASN.0000048223.05219.E4

10.1046%2Fj.1523-1755.2003.00300.x

10.1046%2Fj.1523-1755.2002.00328.x

10.1016%2FS0014-2999%2802%2902619-5

10.1681%2FASN.2005121375

10.1254%2Fjphs.FMJ05003X5

10.1016%2Fj.ejphar.2004.10.040

10.1111%2Fj.1440-1797.2007.00876.x

10.1097%2F01.ASN.0000039568.93355.85

10.1038%2F40187

10.1016%2FS0014-2999%2802%2902929-1

10.1126%2Fscience.275.5304.1308

10.1073%2Fpnas.122228799

10.1007%2Fs00441-006-0365-3

10.1159%2F000078406

10.1681%2FASN.2005050571

10.1681%2FASN.2005020167

10.1046%2Fj.1523-1755.2000.00044.x

10.1006%2Fabio.1976.9999

10.1073%2Fpnas.92.8.3521

10.1159%2F000092196

10.1074%2Fjbc.271.43.26739

10.1038%2Fsj.ki.5001830

10.1681%2FASN.2005090983

10.1046%2Fj.1523-1755.2000.00308.x

10.1097%2F01.ASN.0000019409.17099.33

10.1159%2F000051271

10.1007%2Fs00467-006-0218-z

10.1097%2F01.ASN.0000090745.85482.06

10.1111%2Fj.1523-1755.2005.00723.x

10.1074%2Fjbc.M204806200

10.1093%2Fhmg%2F10.1.1

10.1097%2F01.ASN.0000016142.29721.22

10.1016%2FS1097-2765%2800%2980057-X

10.1172%2FJCI200318242

10.1038%2Fnature04662

10.1172%2FJCI27414

10.1074%2Fjbc.M301689200

10.1073%2Fpnas.0602587103

10.1128%2FMCB.21.14.4829-4836.2001

10.1073%2Fpnas.96.14.7962

10.1074%2Fjbc.M301279200

10.1097%2F01.ASN.0000057853.05686.89

10.1124%2Fjpet.301.2.459

10.1016%2F0014-2999%2893%2990609-L

10.1152%2Fajpcell.00198.2004

10.1016%2FS0014-2999%2801%2900773-7

10.1016%2F0002-9343%2886%2990930-7

10.1046%2Fj.1523-1755.1999.00450.x

10.1093%2Fndt%2F13.12.3043

10.1038%2Fki.1991.115

10.1681%2FASN.2005121366

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Kidney and Blood Pressure Research

Tập 31 Số 2

111-121

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