Related Experiment Video

Updated: Aug 13, 2026

Acute Myocardial Infarction in Rats
07:45

Acute Myocardial Infarction in Rats

Published on: February 16, 2011

Regulation of interleukin-1beta -induced platelet-derived growth factor receptor-alpha expression in rat pulmonary

Y Z Wang1, P Zhang, A B Rice

  • 1Laboratory of Pulmonary Pathobiology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA.

The Journal of Biological Chemistry
|May 16, 2000
PubMed

Insights

p38 mitogen-activated protein (MAP) kinase regulates platelet-derived growth factor receptor-alpha (PDGF-Ralpha) expression. It signals the synthesis of an mRNA-stabilizing protein, impacting PDGF-Ralpha levels and cell growth.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Biochemistry

Background:

  • Platelet-derived growth factor receptor-alpha (PDGF-Ralpha) plays a crucial role in cell proliferation and is implicated in various fibrotic diseases.
  • Interleukin-1beta (IL-1beta) is a pro-inflammatory cytokine known to influence gene expression in various cell types.

Purpose of the Study:

  • To investigate the role of p38 mitogen-activated protein (MAP) kinase in the regulation of PDGF-Ralpha gene expression in rat pulmonary myofibroblasts.
  • To elucidate the molecular mechanisms by which p38 MAP kinase influences PDGF-Ralpha expression.

Main Methods:

  • Primary rat pulmonary myofibroblasts were cultured and treated with IL-1beta.
  • p38 MAP kinase activity was inhibited using the specific inhibitor SB203580.
  • PDGF-Ralpha mRNA and protein levels were quantified using RT-PCR and Western blotting.
  • Cell surface binding of PDGF-AA and PDGF-AA-stimulated DNA synthesis were assessed.
  • mRNA stability was evaluated using actinomycin D, and protein synthesis requirement was tested with cycloheximide.

Main Results:

  • p38 MAP kinase was constitutively expressed and activated by IL-1beta in myofibroblasts.
  • SB203580 inhibited IL-1beta-induced upregulation of PDGF-Ralpha mRNA and protein in a dose-dependent manner.
  • SB203580 significantly reduced PDGF-AA binding sites and blocked PDGF-AA-stimulated DNA synthesis.
  • p38 MAP kinase inhibition stabilized PDGF-Ralpha mRNA, indicating regulation at the translational level.
  • De novo protein synthesis was required for PDGF-Ralpha mRNA stabilization.

Conclusions:

  • p38 MAP kinase plays a critical role in regulating PDGF-Ralpha expression in pulmonary myofibroblasts.
  • The mechanism involves signaling the synthesis of an mRNA-stabilizing protein, affecting PDGF-Ralpha mRNA stability.
  • These findings highlight p38 MAP kinase as a potential therapeutic target for conditions involving PDGF-Ralpha dysregulation.

More Related Videos

Visualization and Quantification of TGFβ/BMP/SMAD Signaling under Different Fluid Shear Stress Conditions using Proximity-Ligation-Assay11:38

Visualization and Quantification of TGFβ/BMP/SMAD Signaling under Different Fluid Shear Stress Conditions using Proximity-Ligation-Assay

Published on: September 14, 2021

Phospholipid Mediator Induced Transformation in Three-Dimensional Cultures08:02

Phospholipid Mediator Induced Transformation in Three-Dimensional Cultures

Published on: July 27, 2022

Related Concept Videos

Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...