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Related Experiment Videos

ERK and p38 MAP kinase are required for rat renal development.

Mariko Hida1, Sayu Omori, Midori Awazu

  • 1Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan.

Kidney International
|March 29, 2002
PubMed
Summary
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p38 mitogen-activated protein (MAP) kinase (p38) and extracellular signal-regulated protein kinase (ERK) are crucial for embryonic kidney development. p38 primarily impacts kidney growth and nephrogenesis, while ERK influences nephrogenesis.

Area of Science:

  • Developmental Biology
  • Molecular Biology
  • Renal Physiology

Background:

  • Extracellular signal-regulated protein kinase (ERK) and p38 mitogen-activated protein (MAP) kinase (p38) are highly expressed in embryonic kidneys.
  • Previous studies established their presence, necessitating investigation into their specific roles during kidney development.

Purpose of the Study:

  • To elucidate the distinct roles of ERK and p38 signaling pathways in embryonic kidney development.
  • To determine the impact of inhibiting these pathways on key developmental processes like growth, branching, and nephrogenesis.

Main Methods:

  • Rat metanephroi from 15-day-old embryos were cultured and treated with specific inhibitors for ERK (PD98059, U0126) and p38 (SB203580).
  • Growth was assessed via surface area and thymidine incorporation; ureteric bud branching and glomerular formation were quantified using specific markers.

Related Experiment Videos

  • Cell proliferation (PCNA) and apoptosis (TUNEL assay, DNA laddering) were analyzed in kidney sections.
  • Main Results:

    • p38 inhibition (SB203580) significantly reduced metanephroi growth and glomerular number, and severely impaired mesenchymal condensate formation.
    • ERK inhibition (MEK inhibitors) led to a marked reduction in glomerular number and tubuloglomerular structures, with increased apoptosis.
    • While p38 inhibition strongly affected overall kidney growth, both pathways were implicated in nephrogenesis, with p38 also playing a role in kidney growth.

    Conclusions:

    • Both ERK and p38 signaling pathways are essential for normal embryonic kidney development.
    • p38 kinase activity is critical for overall kidney growth and the formation of nephrogenic structures.
    • ERK signaling contributes to nephrogenesis, while p38 is vital for both kidney growth and nephrogenesis.