Related Experiment Video

Updated: Aug 2, 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

Activation of TGF-beta-Smad signaling pathway following polyamine depletion in intestinal epithelial cells

Lan Liu1, Rachel Santora, Jaladanki N Rao

  • 1Dept. of Surgery, Baltimore Veterans Affairs Medical Center, 10 North Greene St., Baltimore, MD 21201, USA.

American Journal of Physiology. Gastrointestinal and Liver Physiology
|July 12, 2003
PubMed

Insights

Cellular polyamine depletion activates Smad proteins, key signaling molecules, by increasing transforming growth factor-beta (TGF-beta) signaling. This leads to stimulated Smad-dependent gene expression and growth arrest in intestinal cells.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Gastrointestinal Physiology

Background:

  • Cellular polyamines are crucial for intestinal mucosal growth and epithelial cell proliferation.
  • Polyamines influence transforming growth factor-beta (TGF-beta) signaling pathways.
  • Smad proteins act as transcription activators in TGF-beta superfamily signaling.

Purpose of the Study:

  • To investigate if Smad proteins are downstream effectors of TGF-beta signaling after polyamine depletion.
  • To elucidate the role of Smads in polyamine-modulated intestinal cell growth and TGF-beta signaling.

Main Methods:

  • Studies were conducted in IEC-6 rat intestinal crypt cells.
  • Cellular polyamines were depleted using alpha-difluoromethylornithine (DFMO).
  • Smad protein levels, nuclear translocation, DNA-binding activity, and transcriptional activation were assessed.
  • TGF-beta signaling was inhibited using antibodies or antisense oligodeoxyribonucleotides.

Main Results:

  • DFMO-induced polyamine depletion increased Smad3 and Smad4 protein levels and nuclear translocation.
  • Polyamine depletion stimulated Smad DNA-binding activity and Smad-dependent promoter activity.
  • Inhibition of Smads or TGF-beta signaling blocked Smad activation and transcriptional activity in polyamine-deficient cells.
  • Polyamine-deficient cells exhibited increased TGF-beta expression and G1 phase growth arrest.

Conclusions:

  • Smad proteins are involved in cellular processes regulated by polyamines.
  • Increased TGF-beta/TGF-beta receptor signaling following polyamine depletion activates Smads.
  • Activated Smads stimulate target gene expression, contributing to growth arrest in polyamine-deficient intestinal cells.

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

Studying the Epithelial Effects of Intestinal Inflammation In Vitro on Established Murine Colonoids06:31

Studying the Epithelial Effects of Intestinal Inflammation In Vitro on Established Murine Colonoids

Published on: June 2, 2023

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...
Renewal of Intestinal Stem Cells01:23

Renewal of Intestinal Stem Cells

The intestinal epithelial lining rapidly renews every 4 to 5 days. The renewal is facilitated by intestinal stem cells (ISCs) located at the base of the crypt– a gland located at the bottom of each villus. ISCs divide asymmetrically to form new stem cells and progenitor daughter cells. The daughter cells are called transit-amplifying (TA) cells which move upwards along the crypt and either differentiate into absorptive cells– the enterocytes or secretory cells– including the goblet,...
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal01:22

Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal

Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...