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Related Concept Videos

The Extracellular Matrix01:29

The 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...
The Extracellular Matrix01:42

The 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.
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 body.
A...
Extracellular Matrix01:26

Extracellular Matrix

Unlike epithelial tissue, which is composed of cells closely packed with little or no extracellular space in between, connective tissue cells are dispersed in a matrix. This extracellular matrix (ECM) is composed of fibrous proteins like collagen, elastin, and fibronectin in a ground substance consisting of interstitial fluid, cell adhesion proteins, and proteoglycans. The proteoglycans form a gel-like material in the spaces between cells and provide hydration, buffering, binding, and force...
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...
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...

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Changes in extracellular matrix composition regulate cyclooxygenase-2 expression in human mesangial cells.

Matilde Alique1, Laura Calleros, Alicia Luengo

  • 1Departamento de Fisiología, Alcala University, Madrid, Spain. matilde.alique@mssm.edu

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Collagen type I increases cyclooxygenase-2 (COX-2) in kidney cells, leading to elevated PGE2. This occurs through the FAK/PI3K/AKT/CREB signaling pathway, highlighting a potential therapeutic target for glomerular diseases.

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Area of Science:

  • Nephrology
  • Molecular Biology
  • Pathology

Background:

  • Glomerular diseases involve abnormal extracellular matrix accumulation, like collagen type I.
  • Eicosanoids from cyclooxygenase-2 (COX-2) play roles in renal disease pathogenesis.
  • Protein kinase B (AKT) signaling influences COX-2 promoter activity.

Purpose of the Study:

  • To investigate the effect of collagen type I on COX-2 expression in human mesangial cells.
  • To elucidate the signaling pathways involved in collagen I-induced COX-2 upregulation.
  • To examine COX-2 and collagen type I expression in a rat model of hypertension.

Main Methods:

  • Human mesangial cells were treated with collagen type I.
  • COX-2 expression, mRNA levels, and PGE2 production were measured.
  • Involvement of focal adhesion kinase (FAK), phosphatidylinositol 3-kinase (PI3K)/AKT, and cAMP response element (CRE) pathways was assessed using inhibitors and Western blotting.
  • COX-2 and collagen type I were analyzed in N-nitro-L-arginine methyl ester (NAME)-induced hypertensive rats.

Main Results:

  • Collagen type I significantly increased COX-2 expression and PGE2 production in human mesangial cells.
  • This upregulation was mediated by increased COX-2 mRNA levels.
  • Collagen I induced FAK activation and activated the PI3K/AKT pathway, which was necessary for COX-2 overexpression.
  • Inhibition of PI3K and AKT blocked collagen I-induced COX-2 upregulation.
  • The cAMP response element (CRE) transcription factor was implicated in the pathway.
  • Elevated COX-2 and collagen type I were observed in the renal tissue and vascular walls of hypertensive rats.

Conclusions:

  • Collagen type I upregulates COX-2 expression in mesangial cells via the FAK/PI3K/AKT/CREB signaling pathway.
  • This mechanism contributes to increased PGE2 production, a factor in glomerular disease.
  • The findings suggest potential therapeutic strategies targeting this pathway in renal diseases characterized by collagen accumulation.