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Related Experiment Videos

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

H T Nguyen1, A A Thomson, B A Kogan

  • 1Department of Urology and Anatomy, University of California School of Medicine, San Francisco, USA.

Laboratory Investigation; a Journal of Technical Methods and Pathology
|March 6, 1999
PubMed
Summary

Complete ureteral obstruction in developing kidneys impairs growth by altering keratinocyte growth factor (KGF) and transforming growth factor-alpha (TGF-alpha) signaling, leading to cystic dysplasia.

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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.

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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.