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Updated: Jul 10, 2026

Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling
07:49

Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling

Published on: August 3, 2018

Mitogenic signaling via platelet-derived growth factor beta in metanephric mesenchymal cells

Brent Wagner1, Jill M Ricono, Yves Gorin

  • 1Division of Nephrology, Department of Medicine, University of Texas Health Science Center, San Antonio, Texas 78229-3900, USA. wagnerb@uthscsa.edu

Journal of the American Society of Nephrology : JASN
|October 19, 2007
PubMed

Insights

Platelet-derived growth factor (PDGF) drives mesenchymal cell growth via PI3-K and reactive oxygen species (ROS) generated by Nox4. This study reveals Nox4

Area of Science:

  • Cell Biology
  • Developmental Biology
  • Molecular Biology

Background:

  • Mesangial cells, crucial for kidney function, are derived from metanephric mesenchymal cells.
  • Platelet-derived growth factor (PDGF) signaling via PDGF receptor beta (PDGFR-beta) is essential for mesangial cell development.
  • PDGF binding to PDGFR-beta activates downstream signaling, including phosphatidylinositol-3-kinase (PI3-K).

Purpose of the Study:

  • To investigate the roles of PI3-K and reactive oxygen species (ROS) in PDGF-mediated signaling in metanephric mesenchymal cells.
  • To elucidate the specific pathways and molecules involved in PDGF-induced cell proliferation.

Main Methods:

  • Utilized cell lines from wild-type and PDGFR-beta knockout (PDGFR-beta -/-) mouse metanephric blastemas.
  • Employed 'add-back' mutant PDGFR-beta in PDGFR-beta -/- cells to study PI3-K dependent effects.
  • Applied antisense oligonucleotides and small interfering RNA to investigate the role of NAD(P)H oxidase Nox4.

Main Results:

  • PDGF is mitogenic for mesenchymal cells expressing PDGFR-beta, with PI3-K regulating DNA synthesis.
  • The MEK-ERK1/2 pathway is partially PI3-K dependent and contributes to PDGF-induced mitogenesis.
  • PDGF-induced DNA synthesis requires ROS generated downstream of PI3-K, with Nox4 identified as the source of these ROS, activating Akt and the MEK-ERK1/2 cascade.

Conclusions:

  • Nox4 is involved in PDGF-induced DNA synthesis in metanephric mesenchymal cells.
  • PDGF-induced PI3-K activity enhances ROS production by Nox4, highlighting a novel signaling mechanism.
  • This study provides critical insights into the molecular regulation of mesangial cell development and kidney organogenesis.

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