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MAP kinase in renal development.

Midori Awazu1, Sayu Omori, Mariko Hida

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

Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association
|October 19, 2002
PubMed
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Mitogen-activated protein kinases (MAPKs) like ERK and p38 are crucial for kidney development. Inhibition of p38 significantly reduced kidney growth and glomerular formation, highlighting its role in nephrogenesis.

Area of Science:

  • Developmental Biology
  • Molecular Biology
  • Renal Physiology

Background:

  • Mitogen-activated protein kinases (MAPKs) regulate cell proliferation and apoptosis.
  • ERK promotes cell growth, while JNK and p38 typically inhibit growth and induce apoptosis.
  • Kidney development involves significant cell proliferation and apoptosis.

Purpose of the Study:

  • Investigate the expression patterns of MAPKs (ERK, JNK, p38) and MKP-1 during kidney development.
  • Determine the roles of ERK and p38 in kidney development using pharmacological inhibitors.

Main Methods:

  • Western blot and immunohistochemistry analyzed MAPK and MKP-1 expression in developing and mature rat kidneys.
  • Rat metanephroi were cultured and treated with MEK inhibitors (PD98059, U0126) or a p38 inhibitor (SB203580).

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  • Metanephroi growth was assessed by surface area and thymidine incorporation; ureteric bud branching and glomerular formation were quantified.

    • Main Results:

    • ERK and p38 expression were high in developing kidneys, while JNK was prominent in adult kidneys.
    • p38 inhibition (SB203580) significantly reduced metanephroi growth and glomerular number.
    • MEK inhibitors (PD98059, U0126) did not affect growth, but U0126 slightly reduced glomerular number; ureteric bud branching was unaffected by inhibitors.

    Conclusions:

    • ERK, p38, and MKP-1 are highly expressed during kidney development, with JNK predominantly in adult kidneys.
    • p38 plays a significant role in kidney growth and nephrogenesis.
    • ERK may also be involved in nephrogenesis, though its role appears less critical than p38 based on these experiments.