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Updated: Oct 13, 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

Role of mitogen-activated protein kinases as downstream effectors of transforming growth factor-beta in mesangial

K Inoki1, M Haneda, T Ishida

  • 1The Third Department of Medicine, Shiga University of Medical Science, Seta, Otsu, Japan.

Kidney International. Supplement
|September 21, 2000
PubMed

Insights

Transforming growth factor-beta (TGF-beta) activates mitogen-activated protein kinases (MAPKs) in mesangial cells. This pathway is crucial for TGF-beta-induced extracellular matrix production, particularly fibronectin.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Transforming growth factor-beta (TGF-beta) is a key cytokine regulating cell functions and extracellular matrix (ECM) production.
  • TGF-beta plays a significant role in fibrotic diseases like glomerulosclerosis, but its signaling pathways are not fully understood.
  • Emerging evidence suggests TGF-beta activates signaling cascades including Smad proteins and mitogen-activated protein kinases (MAPKs).

Purpose of the Study:

  • To investigate the role of MAPKs in TGF-beta-induced ECM gene expression in mesangial cells.
  • To determine if MAPK activation mediates TGF-beta's effects on fibronectin production.

Main Methods:

  • Rat mesangial cells were treated with TGF-beta.
  • Mitogen-activated protein kinase (MAPK) activity, specifically extracellular signal-regulated kinase (ERK), was measured.
  • Fibronectin mRNA and protein expression levels were quantified.
  • The effect of PD98059, a MAPK/ERK kinase (MEK) inhibitor, on fibronectin expression was assessed.

Main Results:

  • TGF-beta significantly increased ERK activity in mesangial cells.
  • TGF-beta treatment led to elevated fibronectin mRNA and protein expression.
  • Inhibition of MEK with PD98059 blocked the TGF-beta-induced increase in fibronectin expression.
  • These findings implicate MAPKs in the TGF-beta signaling pathway.

Conclusions:

  • Mitogen-activated protein kinases (MAPKs), specifically the ERK pathway, are essential mediators of TGF-beta-induced extracellular matrix production in mesangial cells.
  • Targeting MAPK signaling may offer therapeutic strategies for fibrotic kidney diseases.
  • This study clarifies a critical signaling cascade in TGF-beta's role in glomerulosclerosis pathogenesis.

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