Related Experiment Video

Updated: Aug 30, 2026

Expression of Transgenes in Native Bladder Urothelium Using Adenovirus-Mediated Transduction
06:01

Expression of Transgenes in Native Bladder Urothelium Using Adenovirus-Mediated Transduction

Published on: October 6, 2022

Epidermal growth factor receptor activation differentially regulates claudin expression and enhances transepithelial

Amar B Singh1, Raymond C Harris

  • 1Department of Medicine, Vanderbilt University, Nashville, Tennessee 37232-4794, USA.

The Journal of Biological Chemistry
|November 1, 2003
PubMed

Insights

Epidermal Growth Factor (EGF) receptor activation alters claudin expression, enhancing tight junction (TJ) integrity in kidney cells. This suggests a role for EGF signaling in maintaining epithelial barrier function and TJ complexity.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Epithelial Biology

Background:

  • Tight junctions (TJs) are crucial for epithelial barrier function, with claudins being key protein components regulating paracellular permeability.
  • Epidermal Growth Factor (EGF) receptor (EGFR) signaling is implicated in epithelial cell proliferation and differentiation, and its overexpression is linked to cancer.
  • The precise role of EGFR signaling in regulating TJ integrity and claudin expression remains largely uncharacterized.

Purpose of the Study:

  • To investigate the impact of EGF-induced EGFR activation on the expression and localization of claudins in polarized epithelial cells.
  • To determine how EGFR signaling influences overall transepithelial electrical resistance, a functional readout of TJ integrity.
  • To elucidate the specific mechanisms by which EGF signaling modulates TJ protein composition.

Main Methods:

  • Utilized polarized Madin-Darby canine kidney II (MDCK II) cells.
  • Administered EGF to activate EGFR signaling.
  • Analyzed claudin expression (claudin-1, -2, -3, -4) and localization via Western blotting and immunofluorescence.
  • Measured transepithelial electrical resistance (TER) as an indicator of TJ function.
  • Assessed expression and localization of other TJ proteins (ZO-1, occludin) and adherens junction proteins (E-cadherin, beta-catenin).

Main Results:

  • EGF treatment significantly reduced claudin-2 expression.
  • EGF treatment increased the expression and induced cellular redistribution of claudin-1, -3, and -4.
  • These changes in claudin expression correlated with a threefold increase in transepithelial resistance.
  • Expression and localization of ZO-1, occludin, E-cadherin, and beta-catenin remained unaltered, indicating selective regulation of claudins.

Conclusions:

  • EGF-induced EGFR activation selectively modulates claudin expression and localization, thereby enhancing TJ integrity and epithelial barrier function.
  • The differential regulation of claudins by EGF signaling plays a critical role in maintaining TJ complexity and epithelial homeostasis.
  • These findings highlight a novel mechanism by which EGFR signaling influences epithelial barrier properties, with potential implications for diseases involving TJ dysfunction.

More Related Videos

Implementing Patch Clamp and Live Fluorescence Microscopy to Monitor Functional Properties of Freshly Isolated PKD Epithelium08:46

Implementing Patch Clamp and Live Fluorescence Microscopy to Monitor Functional Properties of Freshly Isolated PKD Epithelium

Published on: September 1, 2015

Functional Assessment of Intestinal Tight Junction Barrier and Ion Permeability in Native Tissue by Ussing Chamber Technique06:43

Functional Assessment of Intestinal Tight Junction Barrier and Ion Permeability in Native Tissue by Ussing Chamber Technique

Published on: May 26, 2021

Related Concept Videos

Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...
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...
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...
Tight Junctions01:29

Tight Junctions

Tight junctions are molecular seals between cells that prevent the leaking of fluids, ions, and other small solutes across cavities and compartments in multicellular organisms. They are mainly composed of claudin and occludin transmembrane proteins, and other proteins such as tricellulin and JAM (junctional adhesion molecule). All these proteins are 4-pass transmembrane proteins, except JAM, which is a single-pass transmembrane protein belonging to the immunoglobulin superfamily. The...
Cadherins in Tissue Organization01:19

Cadherins in Tissue Organization

The cadherins are a superfamily of cell adhesion molecules comprising over 180 variants, with specific tissues expressing a particular combination of cadherin types. Cadherins generally exhibit homophilic binding; i.e., cadherins on one cell bind to cadherins of the same or closely related type on another cell. Thus, cells of the same type have a specific affinity to bind to each other and sort themselves into clusters to form tissues.
Cell Sorting During Development
Cell sorting plays an...
Cell-matrix's Response to Mechanical Forces01:13

Cell-matrix's Response to Mechanical Forces

In animal cells, the extracellular matrix allows cells within tissues to withstand external stresses and transmits signals from the outside of the cell to the inside. The extracellular matrix is extensive, and its composition varies between different types of tissues. For example, the reticular fibers and ground substance make up the ECM in loose connective tissue, while collagen and bone minerals make up the ECM of bone tissue. 
Anchoring junctions mechanically attach a cell to the...