Postnatal regulation of 15-hydroxyprostaglandin dehydrogenase in the rat kidney
Postnatal regulation of 15-hydroxyprostaglandin dehydrogenase in the rat kidney
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DOI：
10.1152/ajprenal.00512.2013
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发表时间：
2014-08-15
影响因子：
4.2
通讯作者：
Yang, Tianxin
中科院分区：
文献类型：
--
作者：
Liu, Ying;Jia, Zhanjun;Yang, Tianxin
环氧合酶2（考克斯-2）在出生后肾脏发育中具有确定的作用。15-羟基前列腺素脱氢酶（15-PGDH）最近被鉴定为考克斯-2的内源性抑制剂，在几种病理条件下限制考克斯-2衍生的前列腺素类的产生。本研究旨在研究大鼠出生后肾脏发育过程中15-PGDH表达的调节，并与考克斯-2进行比较。qRT-PCR和免疫印迹结果表明，15-PGDH mRNA和蛋白在新生儿肾脏中就已存在，在出生后第2周达到高峰，随后急剧下降，到成年时已降至极低水平。免疫组化显示，在出生后第二周，肾脏15-PGDH蛋白主要存在于近端小管中，Na/H交换器3和刷状缘（高碘酸-希夫）染色阳性，而考克斯-2蛋白仅限于黄斑致密区和邻近的粗升支。有趣的是，在出生后第4周，15-PGDH蛋白重新分布到厚的上升肢体染色阳性的Na-K-2Cl协同转运。6周龄后，15-PGDH蛋白被发现在近端小管亚群的颗粒。总体而言，这些结果支持15-PGDH可能通过与考克斯-2相互作用调节出生后肾脏发育的可能性。
Cyclooxygenase 2 (COX-2) has an established role in postnatal kidney development. 15-Hydroxyprostaglandin dehydrogenase (15-PGDH) is recently identified as an endogenous inhibitor of COX-2, limiting the production of COX-2-derived prostanoids in several pathological conditions. The present study was undertaken to examine the regulation of renal 15-PGDH expression during postnatal kidney development in rats compared with COX-2. qRT-PCR and immunoblotting demonstrated that 15-PGDH mRNA and protein in the kidney were present in neonates, peaked in the second postnatal week, and then declined sharply to very low level in adulthood. Immunostaining demonstrated that at the second postnatal week, renal 15-PGDH protein was predominantly found in the proximal tubules stained positive for Na/H exchanger 3 and brush borders (periodic acid-Schiff), whereas COX-2 protein was restricted to macular densa and adjacent thick ascending limbs. Interestingly, in the fourth postnatal week, 15-PGDH protein was redistributed to thick ascending limbs stained positive for the Na-K-2Cl cotransporter. After 6 wk of age, 15-PGDH protein was found in the granules in subsets of the proximal tubules. Overall, these results support a possibility that 15-PGDH may regulate postnatal kidney development through interaction with COX-2.