Calcineurin A-α but not A-β is required for normal kidney development and function
Calcineurin A-α but not A-β is required for normal kidney development and function
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DOI：
10.1016/s0002-9440(10)63430-x
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发表时间：
2004-11-01
影响因子：
6
通讯作者：
Barnes, JL
中科院分区：
文献类型：
--
作者：
Gooch, JL;Toro, JJ;Barnes, JL
钙调神经磷酸酶是肾脏中重要的信号分子，可能参与多种过程。钙调神经磷酸酶（CnA）的磷酸酶亚基有三种亚型，α，β和γ。在这项研究中，我们研究了钙调神经磷酸酶A-α（CnA-α）或钙调神经磷酸酶A-β（CnA-β）的损失对肾脏发育和功能的影响。在CnA-α-/-和CnA-β-/-小鼠的全肾匀浆中，总钙调磷酸酶表达和活性显著降低。CnA-β-/-小鼠的肾脏表现正常，小鼠发育无表型异常。相反，CnA-α-/-动物肾脏不能完全发育。特别是生肾区（NZ）的出生后成熟是有缺陷的。在新西兰，肾小球也不能成熟，缺乏系膜细胞。除了发育的改变之外，NZ中没有增殖和细胞死亡增加，CnA-α丢失。最后，与野生型同窝仔相比，在CnA-α-/-动物中观察到胶原沉积增加，血清肌酐水平显著增加，表明肾功能受损。总之，CnA-α而不是CnA-β的缺乏导致NZ和肾小球正常成熟的缺陷、细胞周期的改变和肾功能受损。
Calcineurin is an important signaling molecule in the kidney and may be involved in a variety of processes. The phosphatase subunit of calcineurin (CnA) has three isoforms, alpha, beta, and gamma. In this study, we investigated the effect of loss of calcineurin A-alpha (CnA-alpha) or calcineurin A-beta (CnA-beta) on the development and function of the kidney. Total calcineurin expression and activity was significantly reduced in whole kidney homogenates from both CnA-alpha -/- and CnA-beta -/- mice. Kidneys of CnA-beta -/- mice appear normal and the mice develop with no phenotypic abnormalities. in contrast, kidneys of CnA-alpha -/- animals fail to fully develop. in particular, postnatal maturation of the nephrogenic zone (NZ) is defective. Within the NZ, glomeruli also fail to mature and lack mesangial cells. In addition to alterations in development, there is an absence of proliferation and an increase of cell death in the NZ with loss of CnA-alpha. Finally, increased collagen deposition is observed and serum creatinine levels are significantly increased in CnA-alpha -/- animals compared to wild-type littermates, indicating that kidney function is impaired. In summary, absence of CnA-alpha but not CnA-beta leads to a defect in normal maturation of the NZ and glomeruli, alterations in the cell cycle, and impaired kidney function.