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The cyclin kinase inhibitor p21WAF1, CIP1 is increased in experimental diabetic nephropathy: potential role in glomerular hypertrophy.

C J Kuan, M al-Douahji and S J Shankland
JASN June 1998, 9 (6) 986-993;
C J Kuan
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M al-Douahji
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S J Shankland
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Abstract

High glucose inhibits mesangial cell proliferation in vitro and induces hypertrophy in mesangial cells in culture and in experimental diabetic nephropathy. Cell growth is ultimately controlled at the level of the cell cycle by cell cycle regulatory proteins. Cell cycle progression requires that cyclin-dependent kinases be activated by cyclins. Cyclin kinase inhibitors (CKI) inactivate cyclin-dependent kinases, causing cell cycle arrest. In the current study, high glucose-induced mesangial cell hypertrophy in vitro is shown to be associated with increased levels of the CKI p21, but not p27. In the streptozotocin model of experimental diabetes in the mouse, glomerular hypertrophy was associated with a selective increase in p21 expression, whereas the levels of the CKI p27 and p57 did not change. Unlike many other forms of glomerular injury, diabetic nephropathy was not associated with increased apoptosis. These results support a role for p21 in causing glomerular cell hypertrophy in diabetic nephropathy.

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Journal of the American Society of Nephrology
Vol. 9, Issue 6
1 Jun 1998
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The cyclin kinase inhibitor p21WAF1, CIP1 is increased in experimental diabetic nephropathy: potential role in glomerular hypertrophy.
C J Kuan, M al-Douahji, S J Shankland
JASN Jun 1998, 9 (6) 986-993;

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The cyclin kinase inhibitor p21WAF1, CIP1 is increased in experimental diabetic nephropathy: potential role in glomerular hypertrophy.
C J Kuan, M al-Douahji, S J Shankland
JASN Jun 1998, 9 (6) 986-993;
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Cited By...

  • Therapeutic Potential of Nrf2 Activators in Streptozotocin-Induced Diabetic Nephropathy
  • Role of PPAR{gamma} in renoprotection in Type 2 diabetes: molecular mechanisms and therapeutic potential
  • Glucosamine induces cell-cycle arrest and hypertrophy of mesangial cells: implication of gangliosides
  • Not Just an Inhibitor: A Role for p21 Beyond The Cell Cycle--"The Truth Is Rarely Pure and Never Simple"
  • Exogenous Attenuation of p21Waf1/Cip1 Decreases Mesangial Cell Hypertrophy as a Result of Hyperglycemia and IGF-1
  • The Lack of Cyclin Kinase Inhibitor p27Kip1 Ameliorates Progression of Diabetic Nephropathy
  • p27Kip1: The "Rosebud" of Diabetic Nephropathy?
  • Comparative Trial of N-Acetyl-Cysteine, Taurine, and Oxerutin on Skin and Kidney Damage in Long-Term Experimental Diabetes
  • Molecular Mechanisms of Diabetic Mesangial Cell Hypertrophy: A Proliferation of Novel Factors
  • Connective Tissue Growth Factor and Regulation of the Mesangial Cell Cycle: Role in Cellular Hypertrophy
  • The Genetics of Hypertension Modifies the Renal Cell Replication Response Induced by Experimental Diabetes
  • The Hypertrophic Effect of Transforming Growth Factor-{beta} is Reduced in the Absence of Cyclin-Dependent Kinase-Inhibitors p21 and p27
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