Related Experiment Video

Updated: Jun 25, 2026

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
06:54

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

TGF-beta effects on airway smooth muscle cell proliferation, VEGF release and signal transduction pathways

Joo Hwa Shin1, Jae Won Shim, Deok Soo Kim

  • 1Department of Pediatrics, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.

Respirology (Carlton, Vic.)
|February 5, 2009
PubMed
Abstract

Insights

Transforming growth factor-beta (TGF-beta) promotes airway remodeling by increasing vascular endothelial growth factor (VEGF) release via the phosphoinositide 3-kinase (PI3K) pathway, not by increasing airway smooth muscle cell proliferation.

Area of Science:

  • Cellular and Molecular Biology
  • Respiratory Medicine
  • Pharmacology

Background:

  • Airway smooth muscle (ASM) cell hyperplasia is a hallmark of airway remodeling.
  • Mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) pathways are crucial in cell proliferation signaling.
  • MAPK encompasses extracellular signal-regulated kinase (ERK), p38MAPK, and c-Jun NH2-terminal kinase (JNK).

Purpose of the Study:

  • To investigate the effect of transforming growth factor-beta (TGF-beta) on ASM cell proliferation.
  • To determine TGF-beta's impact on vascular endothelial growth factor (VEGF) release from ASM cells.
  • To elucidate the role of specific signaling pathways, including MAPK and PI3K, in TGF-beta-mediated effects on ASM cells.

Main Methods:

  • ASM cells were growth-arrested and subsequently stimulated with platelet-derived growth factor (PDGF), TGF-beta, and dexamethasone.
  • Specific inhibitors for MAPK (PD98059), PI3K (wortmannin), and JNK (SP600125) were used.
  • Cell proliferation and VEGF concentrations were quantified to assess treatment effects.

Main Results:

  • TGF-beta did not increase ASM cell proliferation, nor did it synergize with PDGF to enhance proliferation.
  • Dexamethasone did not inhibit ASM cell proliferation.
  • TGF-beta significantly augmented VEGF release in a time-dependent manner, further enhanced by co-stimulation with PDGF. Dexamethasone suppressed VEGF release.
  • TGF-beta stimulated PI3K phosphorylation, while PDGF activated both ERK and PI3K phosphorylation. Wortmannin inhibited VEGF release induced by both TGF-beta and PDGF.

Conclusions:

  • TGF-beta may contribute to airway remodeling by promoting VEGF release.
  • The PI3K pathway is implicated in TGF-beta-induced VEGF release.
  • TGF-beta's role in airway remodeling appears to be mediated through VEGF release rather than direct ASM cell proliferation.

More Related Videos

Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling07:49

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

Published on: August 3, 2018

Development of an In Vitro Assay to Evaluate Contractile Function of Mesenchymal Cells that Underwent Epithelial-Mesenchymal Transition06:02

Development of an In Vitro Assay to Evaluate Contractile Function of Mesenchymal Cells that Underwent Epithelial-Mesenchymal Transition

Published on: June 10, 2016

Related Concept Videos

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...
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...
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...
Activation and Inactivation of G Proteins01:22

Activation and Inactivation of G Proteins

Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high affinity and are together...
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
Two...
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...