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BMP7 controls collecting tubule cell proliferation and apoptosis via Smad1-dependent and -independent pathways

T D Piscione1, T Phan, N D Rosenblum

  • 1Division of Nephrology, Program in Developmental Biology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada M5G 1X8.

American Journal of Physiology. Renal Physiology
|January 3, 2001
PubMed

Insights

Bone morphogenetic protein-7 (BMP7) influences kidney collecting duct development differently based on dose. Low-dose BMP7 promotes cell growth, while high-dose BMP7 inhibits growth and triggers cell death via Smad1 pathways.

Area of Science:

  • Nephrology
  • Developmental Biology
  • Molecular Biology

Background:

  • Bone morphogenetic protein-7 (BMP7) is known to regulate kidney development.
  • Understanding BMP7's precise role in collecting duct morphogenesis is crucial for developmental biology.

Purpose of the Study:

  • To elucidate the dose-dependent cellular and molecular mechanisms of BMP7 in kidney collecting duct development.
  • To investigate the role of Smad1 signaling in BMP7-mediated effects.

Main Methods:

  • Utilized embryonic kidney explants and the mIMCD-3 cell line for collecting tubule morphogenesis studies.
  • Administered varying doses of BMP7 (0.25 nM and 10 nM) to assess effects on cell proliferation and apoptosis.
  • Analyzed Smad1 activation and utilized Smad1 dominant-negative mutants to define signaling pathways.

Main Results:

  • Low-dose BMP7 (0.25 nM) significantly increased tubule number and cell proliferation.
  • High-dose BMP7 (10 nM) inhibited cell proliferation and induced apoptosis, similar to BMP2.
  • High-dose BMP7 activated Smad1, and its inhibitory effects were Smad1-dependent, while low-dose effects were not fully Smad1-dependent.

Conclusions:

  • BMP7 exerts dose-dependent control over ureteric bud and collecting duct cell proliferation and apoptosis.
  • BMP7 signaling involves both Smad1-dependent and Smad1-independent pathways in kidney development.

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