Molecular basis for MMP9 induction and disruption of epithelial cell-cell contacts by galectin-3

Jerome Mauris1, Ashley M Woodward1, Zhiyi Cao2

  • 1Schepens Eye Research Institute and Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA.

Insights

Galectin-3 binding protein promotes epithelial cell detachment by inducing matrix metalloproteinase (MMP) expression. This process is crucial for cell motility during tissue repair and cancer spread.

Area of Science:

  • Cell Biology
  • Biochemistry
  • Molecular Biology

Background:

  • Dynamic cell-cell contact modulation is vital for epithelial functions like tissue repair and cancer metastasis.
  • Matrix metalloproteinases (MMPs) degrade extracellular matrix and disrupt intercellular junctions, facilitating cell movement.

Purpose of the Study:

  • To investigate the role of galectin-3 in regulating cell-cell detachment and MMP activity in epithelial tissues.
  • To elucidate the molecular mechanism by which galectin-3 influences cell-cell adhesion and MMP induction.

Main Methods:

  • Utilized the cornea as a model system.
  • Investigated galectin-3's effect on cell-cell detachment and occludin redistribution.
  • Examined galectin-3's interaction with CD147 (EMMPRIN) to induce MMP expression.
  • Employed galectin-3-knockout mice for in vivo wound healing studies.

Main Results:

  • Galectin-3, via its N-terminal domain, promotes epithelial cell detachment and occludin redistribution.
  • Galectin-3 induces MMP expression through interaction and clustering of cell surface CD147.
  • In vivo, galectin-3 regulates MMP9 synthesis at the leading edge of migrating epithelium during wound healing.

Conclusions:

  • Established a novel galectin-3-mediated mechanism for inducing metalloproteinase expression.
  • Demonstrated galectin-3's role in disrupting cell-cell contacts essential for epithelial cell motility.
  • Highlighted galectin-3 as a key regulator in processes requiring epithelial cell migration.

Related Concept Videos

Role of Matrix Metalloproteases in Degradation of ECM01:23

Role of Matrix Metalloproteases in Degradation of ECM

Matrix metalloproteases (MMPs) are enzymes involved in the hydrolysis of proteins and glycoproteins of the extracellular matrix. MMPs are essential for the migration and proliferation of cells through the dense matrix network, throughout embryonic development, and throughout morphogenesis. The first MMP activity discovered was a collagenase in a tadpole's tail undergoing metamorphosis. The active collagen deposition and modifications lead to the morphogenesis of tadpoles into the adult...
2.9K
Overview of Cell-Matrix Interactions01:24

Overview of Cell-Matrix Interactions

The extracellular matrix or ECM holds cells together to form a tissue and allows the cells within the tissue to communicate. ECM comprises proteins such as fibronectin, collagen, laminin, etc. The most abundant protein in this space is collagen. Collagen fibers are interwoven with carbohydrate-containing protein molecules called proteoglycans. ECM allows cell migration and provides a structural scaffold at cell adhesion that anchors the cell when the extracellular matrix proteins interact with...
8.0K
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...
2.7K
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...
2.8K
Matrix Proteoglycans and Glycoproteins01:21

Matrix Proteoglycans and Glycoproteins

Proteoglycans are extensively glycosylated proteins, commonly found in the extracellular matrix, interwoven with collagen fibers. Hyaline cartilage, the most common type of cartilage in the body, consists of short and dispersed collagen fibers associated with large amounts of proteoglycans. These proteoglycans have long negative charges that attract cations, which in turn attract water molecules. This influx of ions and water molecules swells up the proteoglycan like a water-soaked gel that can...
4.3K