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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

TGF-beta1 induces COX-2 expression and PGE2 synthesis through MAPK and PI3K pathways in human mesangial cells

A Rodríguez-Barbero1, F Dorado, S Velasco

  • 1Departamento de Fisiología y Farmacología, Instituto Reina Sofía de Investigación Nefrológica, Universidad de Salamanca, Campus Miguel de Unamuno, Edificio Departamental, Salamanca, Spain.

Kidney International
|July 6, 2006
PubMed

Insights

Transforming growth factor-beta1 (TGF-beta1) activates cyclooxygenase-2 (COX-2) in human mesangial cells, increasing prostaglandin E2. This pathway involves mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) signaling, offering new therapeutic targets for kidney diseases.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Immunology

Background:

  • Transforming growth factor-beta1 (TGF-beta1) is implicated in renal disease progression.
  • Eicosanoids from cyclooxygenase-2 (COX-2) are involved in immune-mediated renal pathologies.
  • Mesangial cells (MC) are key players in kidney function and disease, expressing TGF-beta1 receptors and inducible COX-2.

Purpose of the Study:

  • To investigate if TGF-beta1 stimulates COX-2 expression in human mesangial cells (HMC).
  • To determine the involvement of mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) cascades in TGF-beta1-induced COX-2 expression.
  • To assess the impact of TGF-beta1 and these signaling pathways on prostaglandin E2 (PGE2) synthesis.

Main Methods:

  • Primary cultures and an immortalized cell line of HMC were utilized.
  • Studies involved assessing COX-2 promoter activity, mRNA, and protein expression.
  • Involvement of signaling pathways was analyzed using pathway inhibitors.

Main Results:

  • TGF-beta1 significantly induced COX-2 promoter activity, mRNA, and protein expression in HMC.
  • TGF-beta1-induced COX-2 expression was associated with increased PGE2 synthesis.
  • Inhibition of extracellular signal-regulated kinase (ERK)1/2, p38 MAPK, and PI3K pathways attenuated TGF-beta1-induced COX-2 overexpression.

Conclusions:

  • TGF-beta1 regulates COX-2 expression in HMC via activation of ERK1/2, p38 MAPK, and PI3K signaling pathways.
  • This molecular mechanism highlights a novel role for TGF-beta1 in controlling COX-2 and PGE2 production in mesangial cells.
  • Understanding this pathway provides insights for developing targeted therapies for glomerular diseases.

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