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Podocyte expression of the CDK-inhibitor p57 during development and disease
K Hiromura1, L A Haseley, P Zhang
1Department of Medicine, Division of Nephrology, University of Washington School of Medicine, Seattle, Washington 98195, USA. stuartjs@u.washington.edu
Kidney International
|December 12, 2001
Summary
Cyclin-dependent kinase inhibitor p57Kip2 (p57) is not essential for podocyte development or differentiation. However, decreased p57 expression in glomerular disease suggests a role for Cip/Kip family members in podocyte proliferation.
Area of Science:
- Nephrology
- Cell Biology
- Developmental Biology
Background:
- Mature podocytes are terminally differentiated cells with limited proliferation.
- The cell cycle proteins regulating podocyte quiescence and re-entry are not fully understood.
- The role of cyclin-dependent kinase (CDK)-inhibitor p57Kip2 (p57) was investigated.
Purpose of the Study:
- To define the role of p57 in podocyte development and disease.
- To investigate p57's function in podocyte cell cycle regulation.
Main Methods:
- Immunohistochemistry of developing mouse kidneys and models of glomerular disease (passive Heymann nephritis, anti-glomerular antibody).
- Analysis of embryonic p57-/- mice for glomerulogenesis.
- In vitro studies of podocyte differentiation and cell cycle regulator expression (p21, p27, p57).
Main Results:
- p57 expression increased during glomerulogenesis, coinciding with reduced podocyte proliferation.
- p57 knockout mice exhibited normal glomerular podocyte development.
- p57 expression decreased in experimental glomerular disease models, particularly in proliferating podocytes.
Conclusions:
- p57 is not essential for podocyte differentiation or normal development.
- Other cell cycle regulators likely play a role in podocyte differentiation.
- Reduced p57 in glomerular disease suggests Cip/Kip family members collectively regulate podocyte proliferation.
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