Growth factor expression in the obstructed developing and mature rat kidney.

Area of Science:

• Nephrology
• Developmental Biology
• Molecular Biology

Background:

• Ureteral obstruction significantly impacts kidney development and function.
• Growth factors and their receptors play critical roles in renal development and response to injury.

Purpose of the Study:

• To investigate the role of keratinocyte growth factor (KGF), transforming growth factor-alpha (TGF-alpha), and their receptors in renal growth alterations caused by ureteral obstruction in developing kidneys.
• To compare the effects of obstruction in neonatal versus adult kidneys.

Main Methods:

• Neonatal and adult rats underwent unilateral ureteral ligation or sham operation.
• Kidneys were harvested at various time points for histological, immunohistochemical, and molecular analyses.
• Measurements included DNA synthesis, cellular proliferation ([3H]thymidine labeling), and mRNA levels of KGF, KGF receptor, TGF-alpha, and EGF receptor via RNase protection assays.

Main Results:

• Neonatal obstruction led to decreased DNA synthesis, parenchymal loss, myofibroblast proliferation, reduced tubular formation, and cystic dysplasia.
• Adult obstruction caused transient medullary ductal cell growth, parenchymal loss, myofibroblast proliferation, and lymphocytic infiltration, but not cystic dysplasia.
• Obstructed neonatal kidneys showed increased mRNA for KGF, KGF receptor, and TGF-alpha; adult kidneys showed delayed, moderate increases in these factors, with no significant change in EGF receptor mRNA.

Conclusions:

• Ureteral obstruction alters the expression of KGF, TGF-alpha, and their receptors during renal development.
• These molecular changes likely contribute to impaired renal growth and abnormal development observed in neonatal ureteral obstruction.
• Increased TGF-alpha expression and cystic dysplasia are unique features of neonatal obstruction compared to adult obstruction.