Angiotensin II-stimulated hypertrophy of LLC-PK1 cells depends on the induction of the cyclin-dependent kinase inhibitor p27Kip1

Kidney International
G Wolf, R A Stahl

Abstract

Angiotensin II (Ang II) induces hypertrophy of cultured proximal tubular epithelial cells including the LLC-PK1 cell line. We have previously shown that this hypertrophy appears in the G1-phase of the cell cycle. Since progression through the cell cycle is controlled by a series of cyclin and cyclin-dependent kinase (CdK) complexes that may be inactivated by CdK inhibitors, we studied the expression of the CdK-inhibitor p27Kip1 in LLC-PK1 cells challenged with Ang II. Compared to cells grown in serum-free medium, Ang II treatment enhanced p27Kip1 protein, but not mRNA expression. This p27Kip1 induction was mediated through AT1-receptors. Exogenous TGF-beta also stimulated p27Kip1 protein expression. Immunoprecipitation experiments revealed that p27Kip1 preferentially associated with CdK4 in Ang II-treated LLC-PK1 cells and that the activity of this kinase was inhibited after Ang II-treatment, an effect that may be generated by increased p27Kip1 binding to cyclin D1-CdK4 complexes. In contrast, p27Kip1 was not associated with cyclin E-CdK2 complexes in Ang II-stimulated cells. Treatment of LLC-PK1 cells with p27Kip1 antisense, but not missense, oligonucleotides abolished the Ang II-mediated cell hypertrophy as measured by de nov...Continue Reading

References

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Citations

Aug 5, 1999·Kidney International·G Wolf, F N Ziyadeh
Oct 3, 1999·Kidney International·G Wolf
Sep 21, 2000·Kidney International. Supplement·G Wolf
Oct 10, 2002·Kidney International·Baolian Liu, Patricia A Preisig
Jun 6, 2003·Kidney International·Gunter WolfRolf A K Stahl
Mar 27, 2009·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Inna SinuaniBenjamin Sredni
Sep 8, 2000·American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation·K D Burns
Dec 16, 1998·Kidney International·S J Shankland
Aug 1, 1997·Kidney International·S J Shankland
Feb 18, 2004·Hypertension·Gunter Wolf, Ulrich O Wenzel
Aug 10, 2007·Journal of the American Society of Nephrology : JASN·Anja Sachse, Gunter Wolf
Jan 15, 2010·American Journal of Physiology. Renal Physiology·Kumiko NishiharaKen-ichi Inui
Oct 21, 2000·American Journal of Hypertension·A KuboK Kanmatsuse
Jun 16, 2001·American Journal of Physiology. Renal Physiology·T HannkenG Wolf
Apr 6, 2000·American Journal of Physiology. Renal Physiology·S J Shankland, G Wolf
Jun 11, 2002·American Journal of Physiology. Cell Physiology·Bradley S DixonMichael J Dennis
Jul 27, 1999·Proceedings of the Association of American Physicians·G WolfR A Stahl
Apr 19, 2002·Journal of the American Society of Nephrology : JASN·Toshiaki MonkawaStuart J Shankland
Feb 22, 2003·Journal of the American Society of Nephrology : JASN·Midori AwazuHisayo Fujita

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