Minuth Will W
Institute of Anatomy, University of Regensburg, 93053, Regensburg, Germany.
Mol Cell Pediatr. 2017 Dec 7;4(1):12. doi: 10.1186/s40348-017-0078-6.
Numerous investigations are dealing with anlage of the mammalian kidney and primary development of nephrons. However, only few information is available about the last steps in kidney development leading at birth to a downregulation of morphogen activity in the nephrogenic zone and to a loss of stem cell niches aligned beyond the organ capsule. Surprisingly, these natural changes in the developmental program display similarities to processes occurring in the kidneys of preterm and low-birth-weight babies. Although those babies are born at a time with a principally intact nephrogenic zone and active niches, a high proportion of them suffers on impairment of nephrogenesis resulting in oligonephropathy, formation of atypical glomeruli, and immaturity of parenchyma. The setting points out that up to date not identified noxae in the nephrogenic zone hamper primary steps of parenchyma development. In this situation, a possible therapeutic aim is to prolong nephrogenesis by medications. However, actual data provide information that administration of drugs is problematic due to an unexpectedly complex microanatomy of the nephrogenic zone, in niches so far not considered textured extracellular matrix and peculiar contacts between mesenchymal cell projections and epithelial stem cells via tunneling nanotubes. Thus, it remains to be figured out whether disturbance of morphogen signaling altered synthesis of extracellular matrix, disturbed cell-to-cell contacts, or modified interstitial fluid impair nephrogenic activity. Due to most unanswered questions, search for eligible drugs prolonging nephrogenesis and their reliable administration is a special challenge for the future.
众多研究都在探讨哺乳动物肾脏的原基以及肾单位的早期发育。然而，关于肾脏发育的最后阶段，即出生时肾发生区形态发生素活性下调以及肾被膜外排列的干细胞龛丧失的相关信息却很少。令人惊讶的是，发育程序中的这些自然变化与早产和低体重儿肾脏中发生的过程存在相似之处。尽管这些婴儿出生时肾发生区基本完整且干细胞龛活跃，但其中很大一部分人患有肾发生受损，导致肾发育不全、非典型肾小球形成以及实质不成熟。这种情况表明，至今尚未确定的肾发生区有害物质阻碍了实质发育的初始步骤。在这种情况下，一个可能的治疗目标是通过药物延长肾发生。然而，实际数据表明，由于肾发生区意外复杂的微观解剖结构，药物给药存在问题，在干细胞龛中存在迄今未被考虑的有纹理的细胞外基质以及间充质细胞突起与上皮干细胞通过隧道纳米管的特殊接触。因此，形态发生素信号传导的紊乱是否改变细胞外基质的合成、干扰细胞间接触或改变间质液从而损害肾发生活性，仍有待弄清楚。由于大多数问题尚未得到解答，寻找能够延长肾发生的合适药物及其可靠给药方法是未来的一项特殊挑战。
