Role of SGK2 in Sodium Transport in the Kidney

SGK2 在肾脏钠转运中的作用

• 批准号: 6691521
• 负责人: ALAN C PAO
• 金额: $ 5.19万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-03-01 至 2006-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6691521
• 关键词: Xenopus oocyte; adrenalectomy; aldosterone; biological transport; dexamethasone; enzyme activity; gene expression; hormone regulation /control mechanism; immunocytochemistry; in situ hybridization; laboratory rat; northern blottings; phosphatidylinositol 3 kinase; phosphotransferases; postdoctoral investigator; protein localization; renal tubule; sodium ion; tissue /cell culture; transfection

DESCRIPTION (provided by applicant): The overall goal of this research proposal is to understand the expression, regulation, and function of serum and glucocorticoid induced kinase 2 (sgk2) and the precise role it plays in sodium (Na+) transport across the nephron. The molecular basis underlying aldosterone-induced Na+ transport in the nephron has not been fully elucidated. Recently, sgk1 has been identified as a central mediator between early aldosterone effects and epithelial Na+ channel-mediated Na+ transport. Even more recently, two additional isoforms of sgk, sgk2 and sgk3, have been discovered. Localization of sgk2 expression and assessment of hormone-mediated sgk2 regulation will be performed through aldosterone and dexamethasone infusion in rats with subsequent sgk2 expression analyses by in situ hybridization and immunocytochemistry. Identification of downstream effectors of sgk2 will be performed through co-expression assays of Xenopus laevis oocytes with sgk2 and nephron segment-specific Na+ co-transporters. Finally, a tetracycline-inducible (Tet-On) sgk2 expression system in A6 cells will be constructed to isolate the specific effects of sgk2 on Na+ transport in a time-dependent manner. Given that inappropriate Na+ handling can result in extracellular fluid volume expansion and hypertension in humans, understanding the signaling pathways mediating aldosterone-induced Na+ transport in the kidney is clinically important.

描述（由申请人提供）：该研究建议的总体目标是了解血清和糖皮质激素诱导的激酶2（SGK2）的表达，调节和功能及其在钠（Na+）跨肾ph子中扮演的精确作用。肾单位中醛固酮诱导的Na+转运的分子基础尚未完全阐明。最近，SGK1已被确定为早期醛固酮效应和上皮Na+通道介导的Na+转运之间的中心介体。最近，已经发现了SGK，SGK2和SGK3的另外两种同工型。 SGK2表达的定位和激素介导的SGK2调节的评估将通过醛固酮和地塞米松输注在随后的SGK2表达分析中，通过原位杂交和不受侵袭性化学的化学进行。 SGK2下游效应子的识别将通过与SGK2和Nephron节段特异性Na+共转运蛋白的爪诺邦LAEVIS卵母细胞共表达测定。最后，将构建A6细胞中四环素诱导（TET-ON）SGK2表达系统，以隔离SGK2对Na+转运的特定效应，以时间依赖性方式。鉴于不适当的Na+处理可能会导致人类的细胞外流体体积的扩张和高血压，因此了解介导醛固酮诱导的肾脏中Na+转运的信号传导途径在临床上很重要。