Université de Paris, Institut Necker-Enfants Malades (INEM), Epigenetics and Development Team, INSERM U1151, CNRS UMR 8253, 75015 Paris, France.
Department of Pathology, Randers Regional Hospital, 8930 Randers, Denmark.
Cell Rep. 2020 Oct 27;33(4):108304. doi: 10.1016/j.celrep.2020.108304.
The architecture of renal glomeruli is acquired through intricate and still poorly understood developmental steps. In our study we identify a crucial glomerular morphogenetic event in nephrogenesis that drives the remodeling/separation of the prospective vascular pole (the future entrance of the glomerular arterioles) and the urinary pole (the tubular outflow). We demonstrate that this remodeling is genetically programmed. In fact, in mouse and human, the absence of HNF1B impairs the remodeling/separation of the two poles, leading to trapping and constriction of the tubular outflow inside the glomerulus. This aberration gives rise to obstructive glomerular dilations upon the initiation of primary urine production. In this context, we show that pharmacological decrease of glomerular filtration significantly contains cystic expansion. From a developmental point of view, our study discloses a crucial event on glomerular patterning affecting the "inside-outside" fate of the epithelia in the renal glomerulus.
肾脏肾小球的结构是通过复杂且仍未被充分理解的发育步骤获得的。在我们的研究中，我们确定了肾发生过程中的一个关键肾小球形态发生事件，该事件驱动了潜在血管极（肾小球小动脉的未来入口）和尿极（管状流出物）的重塑/分离。我们证明了这种重塑是遗传编程的。事实上，在小鼠和人类中，HNF1B 的缺失会损害两极的重塑/分离，导致管状流出物在肾小球内被捕获和收缩。这种异常会导致原发性尿液产生时出现阻塞性肾小球扩张。在这种情况下，我们表明肾小球滤过率的药理学降低可显著抑制囊状扩张。从发育的角度来看，我们的研究揭示了一个影响肾脏肾小球上皮细胞“内外”命运的关键事件。
