p120 catenin is required for normal renal tubulogenesis and glomerulogenesis

Denise K Marciano1, Paul R Brakeman, Chao-Zong Lee

  • 1Department of Medicine, University of California, San Francisco, CA 94158, USA. denise.marciano@utsouthwestern.edu

Development (Cambridge, England)
|April 28, 2011
PubMed

Insights

Absence of p120 catenin (p120ctn) in developing kidneys causes abnormal tubule and glomeruli formation, leading to polycystic kidney disease. This cadherin regulator is crucial for controlling tubule diameter and kidney development.

Area of Science:

  • Nephrology
  • Developmental Biology
  • Cell Biology

Background:

  • Polycystic kidney disease (PKD) is linked to defects in renal tubule diameter regulation.
  • Cadherin regulators play a role in maintaining epithelial structure and function.

Purpose of the Study:

  • To investigate the role of p120 catenin (p120ctn) in early kidney development and its potential link to polycystic kidney disease.
  • To elucidate the molecular mechanisms by which p120ctn influences tubule morphogenesis and diameter control.

Main Methods:

  • Utilized a mouse model with conditional deletion of p120ctn in the renal mesenchyme.
  • Performed p120ctn knockdown in renal epithelial cells cultured in 3D.
  • Analyzed kidney morphology, tubule diameter, cellular proliferation, and cadherin/RhoA levels.

Main Results:

  • Absence of p120ctn led to decreased cadherin levels, abnormal early tubule and glomerular structures.
  • Mutant mice developed cystic kidney disease with increased tubule diameter and proliferation, specifically in proximal tubules.
  • p120ctn knockdown in vitro phenocopied the cystic phenotype, with reduced E-cadherin and active RhoA, and E-cadherin knockdown mimicked these effects.

Conclusions:

  • p120ctn is essential for proper early tubule and glomerular morphogenesis.
  • p120ctn regulates renal tubule diameter, likely via controlling cadherin levels.
  • These findings highlight p120ctn as a critical factor in kidney development and a potential therapeutic target for polycystic kidney disease.

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