Submitted on August 1, 2007
Accepted on September 5, 2007
Developmental Regulation of Calcineurin Isoforms in the Rodent Kidney: Association with COX-2
Haiying Liu1, Wenling Ye1, Guangju Guan2, Zheng Dong3, Zhanjun Jia1, and Tianxin Yang1*
1 Medicine, University of Utah and Veterans Affairs Medical Center, Salt Lake City, Utah, United States
2 Nephrology, Shandong University Medical School, Jinan, Shandong, China
3 Cellular Biology and Anatomy, Medical College of Georgia, Augusta, Georgia, United States
* To whom correspondence should be addressed. E-mail: tianxin.yang{at}hsc.utah.edu.
Calcineurin A
(Cn-A)-deficient mice develop abnormalities of postnatal kidney development, similar to that of COX-2-deficient mice. The present study was undertaken to examine expression and regulation of Cn isoforms in the developing kidney during the postnatal period and further characterize the relationship between Cn and COX-2. The protein expressions of all three Cn isoforms, including Cn-A, -A
, and -B, as determined by immunoblotting, increased in parallel in the first postnatal week and declined gradually with age. Renal Cn-A and -A mRNA expressions were both developmentally regulated in the same fashion as their protein expressions while renal Cn-B1 mRNA was not obviously induced in the first postnatal week. Immunohistochemistry demonstrated colocalization of Cn-A, Cn-A, and COX-2 in the same cells of thick ascending limb and macula densa. Administration with CsA (2.5 mg/kg/d) during the postnatal period remarkably suppressed renal COX-2 expression as assessed by both immunoblotting and immunohistochemistry. Deletion of Cn-A but not Cn-A in mice significantly reduced renal COX-2 expression at the postnatal period. Together, these data suggest that renal Cn isoforms are subject to normal developmental regulation and they may play a role in postnatal kidney development via interaction with COX-2.
