Expression of ERK1/2, p38, and JNK in Normal Kidney Development and CAKUT

TL;DR

This study examines how specific proteins involved in kidney development differ in normal and abnormal fetal kidneys, offering insights into the causes of congenital kidney defects.

Contribution

The study reveals distinct expression patterns of ERK1/2, p38, and JNK in normal and CAKUT-affected fetal kidneys, linking them to specific developmental phases and anomalies.

Findings

ERK1/2 expression increased in late development in normal kidneys but was reduced in hypoplastic kidneys.

p38 showed early upregulation in dysplastic kidneys and late elevation in horseshoe kidneys.

JNK was significantly upregulated in horseshoe kidneys during specific developmental phases.

Abstract

Background and Objectives: Mitogen-activated protein kinases (p38, JNK, ERK1/2) regulate key cellular processes essential for kidney development. Disruptions in these signaling pathways can lead to congenital anomalies of the kidney and urinary tract (CAKUT), a major cause of pediatric kidney disease. This study investigates and compares the expression of these molecules in normal fetal kidneys and CAKUT-affected tissues. Materials and Methods: Forty-three human fetal kidney samples, including controls and specimens with horseshoe, hypoplastic, and dysplastic kidneys, were analyzed across developmental phases 2–4 using immunofluorescence. Quantitative image analysis and statistical comparisons were performed between developmental stages and phenotypes. Results: ERK1/2 expression increased during late development in control kidneys but was significantly reduced in hypoplastic kidneys. p38 showed phase-dependent alterations, with early upregulation in dysplastic kidneys and late elevation in horseshoe kidneys. JNK exhibited significant phase-dependent upregulation in horseshoe kidneys. P38 displayed dynamic expression associated with nephron maturation. Conclusions: MAPK pathways show distinct developmental and phenotype-specific expression patterns in human fetal kidneys. These differences reflect divergent pathogenic mechanisms in CAKUT and may support improved molecular characterization of congenital renal anomalies.

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