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Related Experiment Video

Updated: Aug 23, 2025

Isolation and Culture of Cells from the Nephrogenic Zone of the Embryonic Mouse Kidney
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Protective role of endorepellin in renal developmental programming.

Xiaoshan Tang1,2, Manqing Sun1,2, Qian Shen1,2

  • 1Department of Nephrology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.

Frontiers in Cell and Developmental Biology
|November 4, 2022
PubMed
Summary

Environmental factors during development can reduce kidney health, leading to chronic kidney disease (CKD). This study shows endorepellin protects against reduced nephron number by inhibiting progenitor cell apoptosis via the ERK1/2 pathway.

Keywords:
apopotosisendorepellinintrauterine growth restrictionnephron endowmentrenal development

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Area of Science:

  • Nephrology
  • Developmental Biology
  • Molecular Medicine

Background:

  • Adverse intrauterine and early postnatal environments impair kidney development, reducing nephron endowment and increasing risk for hypertension and chronic kidney disease (CKD).
  • Enhanced glomerular progenitor cell apoptosis is a key mechanism in this renal developmental programming.
  • Perlecan, an extracellular matrix glycoprotein, and its domain V (endorepellin) were previously identified as differentially expressed proteins.

Purpose of the Study:

  • To investigate the role of endorepellin in mitigating kidney developmental defects caused by adverse environments.
  • To explore the mechanism by which endorepellin exerts its protective effects on nephrogenesis.

Main Methods:

  • Utilized explanted mouse embryonic metanephros to assess endorepellin's effect on malnutrition-induced glomeruli-deficit.
  • Employed an in vivo renal developmental programming model using a low-protein diet during pregnancy.
  • Investigated the impact of endorepellin on glomerular progenitor cell apoptosis and ERK1/2 phosphorylation.

Main Results:

  • Endorepellin rescued the glomeruli-deficit phenotype in explanted embryonic kidneys exposed to malnutrition.
  • In vivo studies confirmed endorepellin's protective effect in a low-protein diet model of renal developmental programming.
  • Endorepellin significantly inhibited glomerular progenitor cell apoptosis, which was associated with ERK1/2 pathway activation.

Conclusions:

  • Endorepellin administration can rescue reduced nephron number in models of renal developmental programming.
  • The protective mechanism likely involves the inhibition of glomerular progenitor cell apoptosis through the ERK1/2 signaling pathway.
  • Targeting endorepellin may offer a therapeutic strategy to prevent CKD development stemming from adverse early-life environments.