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Cathespin H is an Fgf10 target involved in Bmp4 degradation during lung branching morphogenesis

Jining Lü1, Jun Qian, Daniel Keppler

  • 1Pulmonary Center, Boston University School of Medicine, Boston, MA 02118, USA.

The Journal of Biological Chemistry
|May 15, 2007
PubMed

Insights

Cathepsin H (Ctsh) regulates bone morphogenetic protein 4 (Bmp4) availability during embryonic lung development. Ctsh controls Bmp4 levels, impacting branching morphogenesis and distal lung patterning.

Area of Science:

  • Developmental Biology
  • Molecular Biology
  • Cell Biology

Background:

  • Fibroblast growth factor 10 (Fgf10) and its receptor Fgfr2b signaling orchestrate lung epithelial development.
  • Downstream targets of Fgf10-Fgfr2b signaling remain incompletely understood.
  • Cathepsin H (Ctsh), a lysosomal cysteine protease, is identified as a novel Fgf10 target in the developing lung epithelium.

Purpose of the Study:

  • To investigate the role of Ctsh in lung development.
  • To elucidate the downstream events regulated by Fgf10-Fgfr2b signaling.
  • To understand the functional relationship between Ctsh and bone morphogenetic protein 4 (Bmp4) during branching morphogenesis.

Main Methods:

  • Global gene expression screening to identify Fgf10 transcriptional targets.
  • Analysis of Ctsh expression in developing lung epithelium.
  • Investigating the spatial and temporal overlap between Ctsh and Bmp4 expression.
  • Functional assays to assess the impact of Ctsh inhibition on Bmp4 levels and lung branching.

Main Results:

  • Ctsh is selectively induced by Fgf10 in the developing lung epithelium.
  • Epithelial Ctsh expression overlaps with Bmp4 during branching morphogenesis.
  • Ctsh activity is crucial for controlling mature Bmp4 protein levels.
  • Inhibition of Ctsh leads to Bmp4 accumulation and disrupted lung branching.

Conclusions:

  • Ctsh acts as a novel regulator of Bmp4 availability during embryonic lung development.
  • Ctsh likely functions via posttranscriptional regulation, potentially proteolyzing Bmp4 to limit its signaling.
  • This mechanism highlights a new pathway controlling Bmp4 activity essential for lung patterning.
  • Ctsh may play a broader role in regulating proteolysis of Bmp4 in other developing organs.

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