Concepts for a therapeutic prolongation of nephrogenesis in preterm and low-birth-weight babies must correspond to structural-functional properties in the nephrogenic zone

Will W Minuth

doi:10.1186/s40348-017-0078-6

Abstract

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.

Highlights

The physiological adaption of a newborn baby to extrauterine life depends on many parameters including an intact morphological and functional development of the kidneys before and after birth [1]
There is an urgent necessity of investigations dealing in human fetal kidney with the synthesis, secretion, and concrete transport of morphogens locally involved in maintenance of stemness and nephrogenesis [9]
This complex task comprises regulation of stemness, cell proliferation, targeted migration, competence, induction, and primary formation of nephrons [9]. This process is active from the beginning of organ anlage up to birth, while in other mammalian species, nephrogenesis can proceed during the early postnatal period [7]. More general tasks such as supervising of survival, stemness, and proliferation of stem cells in the nephrogenic zone is triggered for example by morphogen mouse double minute 2 homolog (Mdm2)

Summary

Introduction

The physiological adaption of a newborn baby to extrauterine life depends on many parameters including an intact morphological and functional development of the kidneys before and after birth [1]. Integrated signaling of morphogens Growth factors or more precisely morphogens are highly bioactive molecules, which control stem cells within the nephrogenic zone and individual niches during development of the kidney [65] This complex task comprises regulation of stemness, cell proliferation, targeted migration, competence, induction, and primary formation of nephrons [9]. This process is active from the beginning of organ anlage up to birth, while in other mammalian species, nephrogenesis can proceed during the early postnatal period [7] More general tasks such as supervising of survival, stemness, and proliferation of stem cells in the nephrogenic zone is triggered for example by morphogen mouse double minute 2 homolog (Mdm). It was demonstrated that separating filters with pore sizes of 0.1 μm and above support induction including tubule formation, while pores of 0.05 μm abolish

Conclusions

Results