Global expression analysis of extracellular matrix-integrin interactions in monocytes
A R de Fougerolles1, G Chi-Rosso, A Bajardi
1Biogen Inc, Cambridge, Massachusetts 02142, USA. tony_de_fougerolles@biogen.com
Immunity
|February 13, 2001
Summary
Cell adhesion to the extracellular matrix (ECM) via integrins significantly impacts gene expression, particularly in immune and inflammatory responses. Growth factors further enhance these ECM-integrin interactions, activating key cellular pathways.
Area of Science:
- Immunology and Cell Biology
- Molecular and Cellular Biology
Background:
- Integrin-mediated cell adhesion to the extracellular matrix (ECM) is crucial for immune and inflammatory processes.
- Understanding how cells respond to their ECM environment is key to deciphering immune regulation.
Purpose of the Study:
- To investigate the impact of ECM-induced cell attachment on monocyte gene expression.
- To determine the role of growth factors in regulating these adhesive events.
- To elucidate the integrin specificity involved in ECM-cell interactions.
Main Methods:
- Utilized a comprehensive and quantitative mRNA profiling technique.
- Analyzed gene expression changes following monocyte adhesion to fibronectin.
- Investigated the potentiation effects of growth factors on adhesion-induced gene expression.
Main Results:
- Cell adhesion to fibronectin upregulated a substantial number of genes.
- Growth factors significantly potentiated the effects of ECM adhesion on gene expression.
- Activated NF-kappaB and Jak/STAT transcription pathways were observed.
- Increased expression of genes associated with inflammatory and immune responses was detected.
Conclusions:
- ECM-integrin interactions play a vital role in regulating immune and inflammatory responses.
- Growth factors amplify the cellular response to ECM adhesion.
- Adhesion-induced activation of transcription pathways highlights the dynamic interplay between cell environment and gene expression.
Related Concept Videos
01:42The Extracellular Matrix
In order to maintain tissue organization, many animal cells are surrounded by structural molecules that make up the extracellular matrix (ECM). Together, the molecules in the ECM maintain the structural integrity of tissue as well as the remarkable specific properties of certain tissues.Composition of the Extracellular MatrixThe extracellular matrix (ECM) is commonly composed of ground substance, a gel-like fluid, fibrous components, and many structurally and functionally diverse molecules.
01:29The Extracellular Matrix
Overview
In order to maintain tissue organization, many animal cells are surrounded by structural molecules that make up the extracellular matrix (ECM). Together, the molecules in the ECM maintain the structural integrity of tissue as well as the remarkable specific properties of certain tissues.
Composition of the Extracellular Matrix
The extracellular matrix (ECM) is commonly composed of ground substance, a gel-like fluid, fibrous components, and many structurally and functionally diverse...
In order to maintain tissue organization, many animal cells are surrounded by structural molecules that make up the extracellular matrix (ECM). Together, the molecules in the ECM maintain the structural integrity of tissue as well as the remarkable specific properties of certain tissues.
Composition of the Extracellular Matrix
The extracellular matrix (ECM) is commonly composed of ground substance, a gel-like fluid, fibrous components, and many structurally and functionally diverse...
01:24Overview 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...
01:10Integrins
Animal and protozoan cells do not have cell walls to help maintain shape and provide structural stability. Instead, these eukaryotic cells secrete a sticky mass of carbohydrates and proteins into the spaces between adjacent cells. This network of proteins and molecules is called an extracellular matrix or ECM.
Some ECM proteins assemble into a basement membrane to which the remaining components adhere. Proteoglycans typically form the bulk of the ECM while fibrous proteins, like collagen,...
Some ECM proteins assemble into a basement membrane to which the remaining components adhere. Proteoglycans typically form the bulk of the ECM while fibrous proteins, like collagen,...
01:15Activation of Integrins
Integrins bind ligands and transmit information from outside the cell to inside or vice-versa through an "outside-in signaling" or "inside-out signaling."
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding events provide an effective stimulus.
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding events provide an effective stimulus.
01:17Intracellular 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.
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