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Updated: Sep 27, 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

Activation of p38 MAPK suppresses matrix metalloproteinase-1 gene expression induced by platelet-derived growth

Hideharu Endo1, Atsushi Utani, Hiroshi Shinkai

  • 1Department of Clinical Biology of Extracellular Matrix (F7), Graduate School of Medicine, Chiba University, 1-8-1, Inohana, Chuo-ku, Japan. chw92121@syd.odn.ne.jp

Archives of Dermatological Research
|March 8, 2003
PubMed

Insights

p38beta2, a specific form of p38 mitogen-activated protein kinase (MAPK), negatively regulates matrix metalloproteinase-1 (MMP-1) gene expression. This finding suggests p38beta2 activation may contribute to skin fibrosis.

Area of Science:

  • Cellular and Molecular Biology
  • Dermatology
  • Biochemistry

Background:

  • p38 mitogen-activated protein kinase (MAPK) plays a role in regulating matrix metalloproteinase-1 (MMP-1) gene expression.
  • The specific role of p38 MAPK isoforms in extracellular matrix regulation within dermal fibroblasts requires further elucidation.

Purpose of the Study:

  • To investigate the activation of p38 MAPK by cytokines involved in extracellular matrix regulation in dermal fibroblasts.
  • To determine the specific p38 MAPK isoforms responsible for regulating MMP-1 gene expression.

Main Methods:

  • Dermal fibroblasts were stimulated with platelet-derived growth factor-BB (PDGF-BB), transforming growth factor-beta, and interleukin-4.
  • p38 MAPK phosphorylation/activation was measured.
  • MMP-1 mRNA levels were assessed in the presence of a p38 MAPK inhibitor.
  • Overexpression of p38alpha and p38beta2 isoforms was performed to evaluate their effect on PDGF-BB-induced MMP-1 promoter activity.

Main Results:

  • PDGF-BB stimulation activated both p38alpha and p38beta2 signaling pathways in dermal fibroblasts.
  • Inhibition of p38 MAPK enhanced PDGF-BB-induced MMP-1 mRNA levels, indicating a negative regulatory role.
  • Overexpression of p38beta2 significantly reduced PDGF-BB-induced MMP-1 promoter activity, whereas p38alpha had no significant effect.

Conclusions:

  • p38beta2 acts as a negative regulator of PDGF-BB-induced MMP-1 expression in dermal fibroblasts.
  • The specific activation of p38beta2 may play a role in the pathogenesis of cutaneous fibrosis.

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