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Am J Physiol Renal Physiol (May 25, 2004). doi:10.1152/ajprenal.00025.2004
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Submitted on January 23, 2004
Accepted on May 21, 2004

Reduced IP receptors in STZ-induced diabetic rat kidneys and high-glucose treated mesangial cells

Rania Nasrallah1 and Richard L. Hebert1*

1 Department of Cellular and Molecular Medicine, Kidney Research Centre, University of Ottawa, Ottawa, ON, Canada

* To whom correspondence should be addressed. E-mail: rlhebert{at}uottawa.ca.

Mesangial cells (MG) are an important source of renal PGE2 and PGI2. The purpose of this study was to examine the effects of cicaprost (CCP: PGI2 analogue) on MG function, and the expression of IP receptors in streptozotocin (STZ)-diabetic rats and glucose-treated MG cells. CCP increased cellular cAMP in immortalized rat MG cells. Both glucose and anisomycin attenuated CCP-cAMP, but not phorbol-myristate-acetate, angiotensin II, or transforming growth factor-{beta}. Also, IP receptor protein was reduced in response to glucose. While CCP decreased the levels of the cell cycle inhibitor p27, it did not alter thymidine or leucine incorporation. However, CCP reduced fibronectin levels by 40 %, and increased matrix metalloproteinase-2 levels by 3- fold, a key enzyme in matrix degradation. Finally, IP receptors were significantly reduced in outer medulla of 4 and 12 wks STZ-diabetic rats; and in the cortex, outer, and inner medullary regions in 6-mth uni-nephrectomized STZ-diabetic rats. The changes in the CCP/IP system observed in this study suggest that IP may serve as an alternate therapeutic target in diabetes.




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