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p38MAPK acts in the BMP7-dependent stimulatory pathway during epithelial cell morphogenesis and is regulated by Smad1

Ming Chang Hu1, David Wasserman, Sunny Hartwig

  • 1Division of Nephrology, Program in Developmental Biology, The Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada.

The Journal of Biological Chemistry
|January 14, 2004
PubMed

Insights

Bone morphogenetic protein-7 (BMP7) stimulates kidney cell development through p38 mitogen-activated kinase (p38 MAPK). Smad1 signaling inhibits this process, revealing a novel regulatory pathway in renal morphogenesis.

Area of Science:

  • Renal Physiology
  • Cell Signaling
  • Developmental Biology

Background:

  • Bone morphogenetic protein-7 (BMP7) has dual effects on kidney development.
  • Previous studies identified activin-like kinase receptors and Smad1 in BMP-dependent inhibition.
  • The role of p38 mitogen-activated kinase (p38 MAPK) in BMP7 signaling was not fully understood.

Purpose of the Study:

  • To investigate the role of p38 MAPK in BMP7-dependent renal epithelial cell morphogenesis.
  • To elucidate the relationship between BMP7, p38 MAPK, and Smad signaling pathways.

Main Methods:

  • Murine inner medullary collecting duct (mIMCD-3) cells were used to study BMP7 effects.
  • p38 MAPK activity and phosphorylation of activating transcription factor 2 (ATF2) were measured.
  • Inhibition of p38 MAPK and manipulation of Smad signaling were employed to assess functional roles.

Main Results:

  • Low doses of BMP7 increased p38 MAPK activity and ATF2 phosphorylation, promoting cell morphogenesis.
  • High doses of BMP7 inhibited p38 MAPK activity.
  • Inhibition of p38 MAPK blocked BMP7-stimulated morphogenesis.
  • Smad1 signaling negatively regulated p38 MAPK activity.

Conclusions:

  • BMP7 stimulates renal epithelial cell morphogenesis through the p38 MAPK pathway.
  • Smad1 negatively regulates p38 MAPK activity, providing a mechanism for BMP7-dependent inhibition.
  • This study reveals a novel signaling axis involving BMP7, p38 MAPK, and Smad1 in kidney development.

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