Related Experiment Video

Updated: Mar 2, 2026

Visualization and Quantification of TGFβ/BMP/SMAD Signaling under Different Fluid Shear Stress Conditions using Proximity-Ligation-Assay
11:38

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

Published on: September 14, 2021

3.9K

Transforming growth factor-beta stimulates intestinal epithelial focal adhesion kinase synthesis via Smad- and

Mary F Walsh1, Dinakar R Ampasala, James Hatfield

  • 1Departments of Surgery and Pathology, John D. Dingell VA Medical Center, Wayne State University, 4646 John R Detroit, MI 48201-1932, USA.

The American Journal of Pathology
|June 28, 2008
PubMed

Insights

Transforming growth factor-beta (TGF-β) increases focal adhesion kinase (FAK) levels near, but not at, ulcer sites in the gut. This regulation of FAK expression is crucial for epithelial cell migration during mucosal healing.

Area of Science:

  • Cell Biology
  • Gastroenterology
  • Wound Healing Research

Background:

  • Focal adhesion kinase (FAK) is vital for cell migration, proliferation, and apoptosis.
  • FAK protein decreases at the edge of migrating gut epithelial cells in vitro.
  • FAK's role in vivo during restitutive gut mucosa healing remained uncharacterized.

Purpose of the Study:

  • To investigate FAK and phospho-FAK expression in human gastric and colonic ulcers in vivo.
  • To determine the role of growth factors, particularly TGF-β, in regulating FAK in gut epithelial cells.
  • To elucidate the signaling pathways involved in TGF-β-mediated FAK regulation.

Main Methods:

  • Immunohistochemical analysis of FAK and phospho-FAK in ulcer tissues.
  • Cell culture experiments using Caco-2 and IEC-6 cells treated with growth factors.
  • Pharmacological inhibition of TGF-β receptors and p38 MAPK.
  • siRNA-mediated gene silencing of Smad2 and p38α.
  • Luciferase reporter assay to measure FAK promoter activity.

Main Results:

  • FAK and phospho-FAK were reduced adjacent to ulcers but increased in epithelia near ulcers.
  • Transforming growth factor-beta (TGF-β) significantly increased FAK levels in gut epithelial cells.
  • TGF-β-induced FAK expression involved Smad2/3 and p38 signaling pathways.
  • FAK(397) levels correlated with total FAK protein expression.

Conclusions:

  • TGF-β upregulates FAK expression near, but not directly at, mucosal ulcer sites in the gut.
  • Smad2/3 and p38 signaling pathways mediate TGF-β's effect on FAK transcription and translation.
  • Regulation of FAK expression, alongside phosphorylation, is critical for gut epithelial cell migration during mucosal repair.

More Related Videos

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

14.6K
Induction and Analysis of Epithelial to Mesenchymal Transition10:37

Induction and Analysis of Epithelial to Mesenchymal Transition

Published on: August 27, 2013

36.6K

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...
10.7K
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...
3.7K
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...
5.9K
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.
2.7K
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...
2.5K
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...
8.8K