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从输尿管芽到首个肾小球:基因、介质与肾脏改变

From ureteric bud to the first glomeruli: genes, mediators, kidney alterations.

作者信息

Fanos Vassilios, Loddo Cristina, Puddu Melania, Gerosa Clara, Fanni Daniela, Ottonello Giovanni, Faa Gavino

机构信息

Department of Surgery, Neonatal Intensive Care Unit, Puericulture Institute and Neonatal Section, Policlinico Monserrato, Azienda Ospedaliera Universitaria di Cagliari, University of Cagliari, 09042, Monserrato, CA, Italy,

出版信息

Int Urol Nephrol. 2015 Jan;47(1):109-16. doi: 10.1007/s11255-014-0784-0. Epub 2014 Sep 9.

Abstract

The development of the mammalian kidney is a complex and in part unknown process which requires interactions between pluripotential/stem cells, undifferentiated mesenchymal cells, epithelial and mesenchymal components, eventually leading to the coordinate development of multiple different specialized epithelial, endothelial and stromal cell types within the kidney architectural complexity. We will describe the embryology and molecular nephrogenetic mechanisms, a fascinating traffic of cells and tissues which takes place in five stages: (1) ureteric bud (UB) development; (2) cap mesenchyme formation; (3) mesenchymal-epithelial transition (MET); (4) glomerulogenesis and tubulogenesis; (5) interstitial cell development. In particular, we will analyze the multiple cell types involved in these dramatic events as characters moving between different worlds, from the mesenchymal to the epithelial world and back, and will start to define the multiple factors that propel these cells during their travels throughout the developing kidney. Moreover, according with the hypothesis of renal perinatal programing, we will present the results reached in the fields of immunohistochemistry and molecular biology, by means of which we can explain how a loss or excess of molecular factors governing nephrogenesis may cause the onset of pathologies of different gravity, in some cases leading to a chronic kidney disease at different times from birth.

摘要

哺乳动物肾脏的发育是一个复杂且部分未知的过程,需要多能/干细胞、未分化间充质细胞、上皮和间充质成分之间相互作用,最终在肾脏结构复杂性内实现多种不同特化上皮、内皮和基质细胞类型的协调发育。我们将描述胚胎学和分子肾发生机制,这是一个在五个阶段发生的细胞和组织的奇妙变化过程:(1)输尿管芽(UB)发育;(2)帽状间充质形成;(3)间充质-上皮转化(MET);(4)肾小球发生和肾小管发生;(5)间质细胞发育。特别是,我们将分析参与这些重大事件的多种细胞类型,它们如同在不同世界间穿梭的角色,从间充质世界到上皮世界再返回,并且将开始确定在发育中的肾脏中推动这些细胞移动的多种因素。此外,根据肾脏围产期编程假说,我们将展示免疫组织化学和分子生物学领域所取得的结果,借此我们可以解释控制肾发生的分子因子的缺失或过量如何可能导致不同严重程度疾病的发生,在某些情况下会在出生后的不同时间引发慢性肾脏病。

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