TY - JOUR
T1 - Developmental regulation of calcineurin isoforms in the rodent kidney
T2 - Association with COX-2
AU - Liu, Haiying
AU - Ye, Wenling
AU - Guan, Gju
AU - Dong, Zheng
AU - Jia, Zhanjun
AU - Yang, Tianxin
PY - 2007/12
Y1 - 2007/12
N2 - Calcineurin (Cn)-Aα-deficient mice develop abnormalities of postnatal kidney development, similar to that of cyclooxygenase (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-Aα, -Aβ, and -B, as determined by immunoblotting, increased in parallel in the first postnatal week and declined gradually with age. Renal Cn-Aα and -Aβ mRNA expressions were both developmentally regulated in the same fashion as their protein expressions, whereas renal Cn-B1 mRNA was not obviously induced in the first postnatal week. Immunohistochemistry demonstrated colocalization of Cn-Aα, Cn-Aβ, and COX-2 in the same cells of thick ascending limb and macula densa. Administration with cyclosporine A (2.5 mg·kg -1·day-1) during the postnatal period remarkably suppressed renal COX-2 expression as assessed by both immunoblotting and immunohistochemistry. Deletion of Cn-Aα but not Cn-Aβ 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.
AB - Calcineurin (Cn)-Aα-deficient mice develop abnormalities of postnatal kidney development, similar to that of cyclooxygenase (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-Aα, -Aβ, and -B, as determined by immunoblotting, increased in parallel in the first postnatal week and declined gradually with age. Renal Cn-Aα and -Aβ mRNA expressions were both developmentally regulated in the same fashion as their protein expressions, whereas renal Cn-B1 mRNA was not obviously induced in the first postnatal week. Immunohistochemistry demonstrated colocalization of Cn-Aα, Cn-Aβ, and COX-2 in the same cells of thick ascending limb and macula densa. Administration with cyclosporine A (2.5 mg·kg -1·day-1) during the postnatal period remarkably suppressed renal COX-2 expression as assessed by both immunoblotting and immunohistochemistry. Deletion of Cn-Aα but not Cn-Aβ 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.
KW - Cyclooxygenase-2
KW - Cyclosporine A
KW - Postnatal kidney development
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U2 - 10.1152/ajprenal.00360.2007
DO - 10.1152/ajprenal.00360.2007
M3 - Article
C2 - 17881460
AN - SCOPUS:36549053001
SN - 0363-6127
VL - 293
SP - F1898-F1904
JO - American Journal of Physiology - Renal Physiology
JF - American Journal of Physiology - Renal Physiology
IS - 6
ER -