Potential role of RGD-binding integrins in mammalian lung branching morphogenesis

Development ◽  
1991 ◽  
Vol 112 (2) ◽  
pp. 551-558 ◽  
Author(s):  
J. Roman ◽  
C.W. Little ◽  
J.A. McDonald
Keyword(s):  
Lung Development ◽  
Branching Morphogenesis ◽  
Integrin Receptors ◽  
Murine Lung ◽  
Cell Matrix ◽  
Matrix Interactions ◽  
Mammalian Lung ◽  
Cell Matrix Interactions ◽  
Lung Branching

Cell-matrix interactions are generally considered critical for normal lung development. This is particularly likely to be true during the glandular stage, when the primitive airways are formed through a process termed branching morphogenesis. Integrins, transmembrane receptors that bind to extracellular matrices, are likely to mediate important interactions between embryonic cells and their matrices during branching morphogenesis. In this report, we examine the role of integrin receptors in this process. Immunohistochemical studies revealed that the integrins VLA 3, VLA 5 and integrin receptors to vitronectin are expressed in the epithelium and/or mesenchyme during the glandular stage of murine lung development. To correlate expression with function, an in vitro model of murine lung branching morphogenesis was utilized to examine branching in the presence of inhibitors of ligand binding to integrin receptors. One such reagent, a hexapeptide containing the RGD (Arg-Gly-Asp) sequence, diminished branching and resulted in an abnormal morphology, whereas a control peptide RGESP (Arg-Gly-Glu-Ser-Pro) had no effect. These findings suggest a critical role for cell-matrix interactions mediated via integrin receptors in early stages of mammalian lung development.

Modified hydroxyethylmethacrylate hydrogels as a modelling tool for the study of cell-substratum interactions

1989 ◽  
Vol 92 (1) ◽  
pp. 111-121
Author(s):  
P.R. Bergethon ◽  
V. Trinkaus-Randall ◽  
C. Franzblau
Keyword(s):  
Cellular Proliferation ◽  
Hydroxyl Groups ◽  
Native Proteins ◽  
Cell Matrix ◽  
Matrix Interactions ◽  
Specific Proteins ◽  
Cell Matrix Interactions ◽  
And Control ◽  
Macromolecular Content

The interactions between cells and their extracellular substratum environment are complex and difficult to study. Defined, synthetic substrata are valuable tools for experimentally determining the role of ionic and receptor-specific interactions between cells and their substrata. Hydrogels have been modified to contain stoichiometrically defined quantities of both positive and negative charge as well as specific proteins. These synthetic surfaces are water-rich matrices that possess hydroxyl groups, positive and negative ionized charges and native proteins, and can be considered as models of extracellular matrices on which an assessment of charge contribution and macromolecular content and specificity can be addressed with respect to cell-matrix interactions. This study shows that simple gels made of polyhydroxyethylmethacrylate do not support the spreading of cells but that the generation of copolymers by the addition of monomers that contain ionizable functional groups, will permit cell spreading. These simple modifications do not lead to cellular proliferation, yet when collagen is entrapped in the hydrogel substratum, proliferation occurs. The proliferative rate of cells grown on collagen-containing surfaces may be modified by altering the stoichiometry of the ionizable polymers used to make the surface. This study describes a synthetic, definable model for the study of cell-substratum interactions and control.

Molecular regulation of cellular invasion— role of gelatinase A and TIMP-2

1996 ◽  
Vol 74 (6) ◽  
pp. 823-831 ◽  
Author(s):  
Anita E. Yu ◽  
Robert E. Hewitt ◽  
David E. Kleiner ◽  
William G. Stetler-Stevenson
Keyword(s):  
Extracellular Matrix ◽  
Matrix Metalloproteinases ◽  
Tissue Inhibitors Of Metalloproteinases ◽  
Gelatinase A ◽  
Cellular Mechanisms ◽  
Cell Matrix ◽  
Matrix Interactions ◽  
The Matrix ◽  
Cell Matrix Interactions

Extracellular matrix (ECM) turnover is an event that is tightly regulated. Much of the coordinate (physiological) or discoordinate (pathological) degradation of the ECM is catalyzed by a class of proteases known as the matrix metalloproteinases (MMPs) or matrixins. Matrixins are a family of homologous Zn atom dependent endopeptidases that are usually secreted from cells as inactive zymogens. Net degradative activity in the extracellular environment is regulated by specific activators and inhibitors. One member of the matrixin family, gelatinase A, is regulated differently from other MMPs, suggesting that it may play a unique role in cell–matrix interactions, including cell invasion. The conversion from the 72 kDa progelatinase A to the active 62 kDa species may be a key event in the acquisition of invasive potential. This discussion reviews some recent findings on the cellular mechanisms involved in progelatinase A activation and, in particular, the role of tissue inhibitor of matrix metalloproteinases-2 (TIMP-2) and transmembrane containing metalloproteinases (MT-MMP) in this process.Key words: tissue inhibitors of metalloproteinases, metalloproteinase, gelatinases, extracellular matrix, activation.

Role of Integrins in Adhesion of Hematopoietic Progenitor Cells.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4263-4263
Author(s):  
Shawdee Eshghi ◽  
Jing Zhang ◽  
Linda G. Griffith ◽  
Harvey F. Lodish
Keyword(s):  
Stem Cell ◽  
Stem Cell Niche ◽  
Fetal Liver ◽  
Hematopoietic Stem ◽  
Cell Matrix ◽  
Hematopoietic Stem Cell Niche ◽  
Matrix Interactions ◽  
Cell Niche ◽  
Cell Matrix Interactions

Abstract The hematopoietic stem cell niche is the set of soluble growth factors, cell-cell and cell-matrix interactions that contribute to stem cell self renewal in the bone marrow. While cytokines and cell-cell interactions have been well documented, cell-matrix interactions in the niche are less understood. Integrins are a class of highly conserved cell adhesion molecules that are important in hematopoietic development and homing. However the specific role of integrins in mediating adhesion to extracellular matrix in the hematopoietic stem cell niche is unknown. The terminal stages of erythropoiesis in the fetal liver provide a good model system with which to develop several of the assays to be used with HSCs. Using flow cytometry, murine fetal liver erythroid progenitors can be separated at four distinct stages of development based on expression of CD71 and Ter119. Further FACS and quantitative PCR analysis revealed that α4β1 integrin is significantly downregulated over the course of erythroid differentiation. Using a centrifugation assay, we determined that this change is accompanied by a loss of adhesion to fibronectin, and that adhesion to fibronectin is blocked by addition of anti-integrin antibodies. Finally, fetal liver progenitor cells adhered to comb co-polymer surfaces engineered to present peptides specifically recognized by α4β1 integrins. By determining the integrin profile expressed by hematopoietic stem cells and measuring stem cell adhesion to ECM in a similar manner, we can begin to understand how these specific interactions present developmental cues important to maintaining the stem cell phenotype in vivo, in addition to leading to design parameters for ex vivo culture systems.

Substrates of Factor XIII-A: roles in thrombosis and wound healing

2012 ◽  
Vol 124 (3) ◽  
pp. 123-137 ◽  
Author(s):  
Victoria R. Richardson ◽  
Paul Cordell ◽  
Kristina F. Standeven ◽  
Angela M. Carter
Keyword(s):  
Wound Healing ◽  
Factor Xiii ◽  
Tissue Repair ◽  
Cross Linking ◽  
Clot Retraction ◽  
Matrix Deposition ◽  
Cell Matrix ◽  
Matrix Interactions ◽  
Cell Matrix Interactions

FXIII (Factor XIII) is a Ca2+-dependent enzyme which forms covalent ϵ-(γ-glutamyl)lysine cross-links between the γ-carboxy-amine group of a glutamine residue and the ϵ-amino group of a lysine residue. FXIII was originally identified as a protein involved in fibrin clot stabilization; however, additional extracellular and intracellular roles for FXIII have been identified which influence thrombus resolution and tissue repair. The present review discusses the substrates of FXIIIa (activated FXIII) involved in thrombosis and wound healing with a particular focus on: (i) the influence of plasma FXIIIa on the formation of stable fibrin clots able to withstand mechanical and enzymatic breakdown through fibrin–fibrin cross-linking and cross-linking of fibrinolysis inhibitors, in particular α2-antiplasmin; (ii) the role of intracellular FXIIIa in clot retraction through cross-linking of platelet cytoskeleton proteins, including actin, myosin, filamin and vinculin; (iii) the role of intracellular FXIIIa in cross-linking the cytoplasmic tails of monocyte AT1Rs (angiotensin type 1 receptors) and potential effects on the development of atherosclerosis; and (iv) the role of FXIIIa on matrix deposition and tissue repair, including cross-linking of extracellular matrix proteins, such as fibronectin, collagen and von Willebrand factor, and the effects on matrix deposition and cell–matrix interactions. The review highlights the central role of FXIIIa in the regulation of thrombus stability, thrombus regulation, cell–matrix interactions and wound healing, which is supported by observations in FXIII-deficient humans and animals.

scholarly journals RGD-Dependent Epithelial Cell-Matrix Interactions in the Human Intestinal Crypt

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Yannick D. Benoit ◽  
Jean-François Groulx ◽  
David Gagné ◽  
Jean-François Beaulieu
Keyword(s):  
Cell Function ◽  
Intestinal Epithelial ◽  
Integrin Receptors ◽  
Cell Microenvironment ◽  
Cell Matrix ◽  
Epithelial Homeostasis ◽  
Intracellular Signals ◽  
Matrix Interactions ◽  
Key Players ◽  
Cell Matrix Interactions

Interactions between the extracellular matrix (ECM) and integrin receptors trigger structural and functional bonds between the cell microenvironment and the cytoskeleton. Such connections are essential for adhesion structure integrity and are key players in regulating transduction of specific intracellular signals, which in turn regulate the organization of the cell microenvironment and, consequently, cell function. The RGD peptide-dependent integrins represent a key subgroup of ECM receptors involved in the maintenance of epithelial homeostasis. Here we review recent findings on RGD-dependent ECM-integrin interactions and their roles in human intestinal epithelial crypt cells.

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