Retinoids and renal development.

C R Burrow
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引用次数: 40

Abstract

Although it has long been appreciated that retinoids play an essential role in kidney organogenesis, it has only recently been recognized that even mild fetal vitamin A deficiency syndromes can result in a reduction in nephron number. Recent studies have also begun to define the cellular and molecular events associated with retinoid actions in the fetal kidney and have demonstrated the essential function of retinoids in branching growth of the ureteric bud. Importantly, characterization of the renal developmental effects of RAR alpha/beta 2 double homozygous mice combined with metanephric organ culture studies have together shown that one essential function of retinoid action in the developing kidney is the maintenance of c-ret expression in the tips of the ureteric bud. However, many other potential retinoid target genes including midkine, sonic hedgehog, Hox d-11, matrix metalloproteinases, and tissue inhibitors of metalloproteinases appear to play important roles in renal development and might be important downstream mediators of retinoid effects in the developing kidney. It can, therefore, be anticipated that important new insights into fetal kidney development will be forthcoming in the near future, as the essential target genes affected by retinoid signal transduction are progressively elucidated.

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类维生素a和肾脏发育。
虽然人们早就认识到类维生素A在肾脏器官发生中起着重要作用,但直到最近才认识到,即使是轻微的胎儿维生素A缺乏综合征也会导致肾单位数量减少。最近的研究也开始确定胎儿肾脏中与类维甲酸作用相关的细胞和分子事件,并证明了类维甲酸在输尿管芽分支生长中的基本功能。重要的是,RAR α / β 2双纯合子小鼠肾脏发育效应的表征结合后肾器官培养研究共同表明,类维a作用在肾脏发育中的一个基本功能是维持输尿管芽尖端c-ret的表达。然而,许多其他潜在的类视黄醇靶基因,包括midkine、sonic hedgehog、Hox d-11、基质金属蛋白酶和金属蛋白酶的组织抑制剂,似乎在肾脏发育中发挥重要作用,可能是发育肾脏中类视黄醇作用的重要下游介质。因此,可以预见的是,随着受类视黄醛信号转导影响的基本靶基因逐渐被阐明,对胎儿肾脏发育的重要新见解将在不久的将来出现。
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