ERK and p38 MAP kinase are required for rat renal development

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.
• 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.