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Functional interface between cathepsins and growth factors in the kidney development

Maria de Fatima Fernandes Vattimo1, Oscar Fernando Pavão Santos

  • 1Nursing School, University of São Paulo, Av Enéas de Carvalho Aguiar, 419, CEP 05403 000, São Paulo, Brazil. nephron@usp.br

Renal Failure
|September 13, 2005
PubMed

Insights

This study reveals that cathepsin S and cathepsin H proteases are differentially expressed during kidney development. Nerve growth factor (NGF) influences cathepsin S expression, while both proteases interact with hepatic growth factor (HGF) in tubulogenesis.

Area of Science:

  • Developmental Biology
  • Molecular Biology
  • Nephrology

Background:

  • Proteases play a crucial role in extracellular matrix remodeling during kidney development (nephrogenesis).
  • Understanding the specific roles of proteases like cathepsin S (CS) and cathepsin H (CH) is vital for comprehending kidney formation.

Purpose of the Study:

  • To investigate the expression patterns of cathepsins S and H during metanephrogenesis.
  • To explore the functional interplay between CS, CH, and growth factors like hepatic growth factor (HGF) and nerve growth factor (NGF).

Main Methods:

  • Embryonic kidney organ culture.
  • Three-dimensional (3D) cell culture using MDCK and IMCD cells.
  • Reverse transcriptase-polymerase chain reaction (RT-PCR) for gene expression analysis.

Main Results:

  • Cathepsin S expression was observed earlier than cathepsin H during nephrogenesis.
  • Nerve growth factor (NGF) antibody inhibited cathepsin S (CS) gene expression in a dose-dependent manner, but not cathepsin H (CH).
  • Inhibitors of CS and CH reduced HGF-induced branching in 3D cell cultures, confirming an interface between these proteases and HGF.

Conclusions:

  • Cathepsins S and H exhibit distinct expression profiles during kidney development.
  • CS and CH are implicated in tubulogenesis, potentially by mediating the actions of growth factors such as NGF and HGF.

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