Related Experiment Video

Updated: Jun 19, 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

Regulation of transforming growth factor-beta-dependent cyclooxygenase-2 expression in fibroblasts

Takayoshi Matsumura1, Toru Suzuki, Kenichi Aizawa

  • 1Departments of Cardiovascular Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.

The Journal of Biological Chemistry
|October 20, 2009
PubMed

Insights

Transforming growth factor-beta (TGF-beta) regulates cyclooxygenase-2 (COX-2) in fibroblasts. This study identifies factors controlling COX-2, revealing new insights into TGF-beta

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Abnormal transforming growth factor-beta (TGF-beta) signaling contributes to diseases like fibrosis and cancer.
  • TGF-beta-induced cyclooxygenase-2 (COX-2) in fibroblasts is crucial for its anti-fibroproliferative effects.
  • Both TGF-beta and COX-2 are implicated in tumor progression, making tumor-associated fibroblasts a key research area.

Purpose of the Study:

  • To identify regulatory factors of TGF-beta-induced COX-2 expression in fibroblasts.
  • To elucidate the mechanisms by which these factors modulate COX-2 levels.
  • To advance understanding of TGF-beta's role in disease pathogenesis.

Main Methods:

  • Proteomic approaches were utilized to identify regulatory factors.
  • Messenger RNA (mRNA) and protein levels of COX-2 were quantified.
  • Functional pathway analysis was performed to determine regulatory mechanisms.

Main Results:

  • TGF-beta up-regulates heterogeneous nuclear ribonucleoprotein A/B (HNRPAB), nucleotide diphosphate kinase A (NDPK A), and nucleotide diphosphate kinase B (NDPK B).
  • HNRPAB enhances COX-2 mRNA and protein levels by inhibiting mRNA degradation, increasing prostaglandin E(2) (PGE(2)) production.
  • NDPK A and NDPK B attenuate COX-2 levels by interfering with TGF-beta-Smad2/3/4 signaling at the receptor level.

Conclusions:

  • A novel regulatory pathway for TGF-beta-induced COX-2 expression in fibroblasts has been identified.
  • HNRPAB acts as a positive regulator, while NDPK A and NDPK B function as negative regulators of COX-2.
  • These findings enhance the understanding of TGF-beta's pathophysiological mechanisms in diseases involving fibroblasts.

More Related Videos

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

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells06:54

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

Published on: October 27, 2020

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...
Introduction to Fibroblasts01:09

Introduction to Fibroblasts

Rudolph Virchow discovered spindle-shaped cells called fibroblasts in 1858. Inactive fibroblasts, called fibrocytes, become activated by various stimuli, such as growth factors and inflammatory cytokines. Activated fibroblasts play a crucial role in wound healing, inflammation, formation of new blood vessels, and cancer progression. Uncontrolled activation of fibroblasts results in fibrosis, the excess deposition of fibrous tissue, which can lead to scarring and affect normal organs. This...
Cell Specific Gene Expression01:58

Cell Specific Gene Expression

Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
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...
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...