scholarly journals Pericyte recruitment during vasculogenic tube assembly stimulates endothelial basement membrane matrix formation

Blood ◽  
2009 ◽  
Vol 114 (24) ◽  
pp. 5091-5101 ◽  
Author(s):  
Amber N. Stratman ◽  
Kristine M. Malotte ◽  
Rachel D. Mahan ◽  
Michael J. Davis ◽  
George E. Davis
Keyword(s):  
Basement Membrane ◽  
Tube Formation ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Collagen Type Iv ◽  
Matrix Assembly ◽  
Matrix Deposition ◽  
Vascular Basement Membrane ◽  
Membrane Matrix ◽  
Type Iv ◽  
Endothelial Basement Membrane

AbstractWe show that endothelial cell (EC)–generated vascular guidance tunnels (ie, matrix spaces created during tube formation) serve as conduits for the recruitment and motility of pericytes along EC ablumenal surfaces to facilitate vessel maturation events, including vascular basement membrane matrix assembly and restriction of EC tube diameter. During quail development, pericyte recruitment along microvascular tubes directly correlates with vascular basement membrane matrix deposition. Pericyte recruitment to EC tubes leads to specific induction of fibronectin and nidogen-1 (ie, matrix-bridging proteins that link together basement membrane components) as well as perlecan and laminin isoforms. Coincident with these events, up-regulation of integrins, α5β1, α3β1, α6β1, and α1β1, which bind fibronectin, nidogens, laminin isoforms, and collagen type IV, occurs in EC-pericyte cocultures, but not EC-only cultures. Integrin-blocking antibodies to these receptors, disruption of fibronectin matrix assembly, and small interfering RNA suppression of pericyte tissue inhibitor of metalloproteinase (TIMP)-3 (a known regulator of vascular tube stabilization) all lead to decreased EC basement membrane, resulting in increased vessel lumen diameter, a key indicator of dysfunctional EC-pericyte interactions. Thus, pericyte recruitment to EC-lined tubes during vasculogenesis is a stimulatory event controlling vascular basement membrane matrix assembly, a fundamental maturation step regulating the transition from vascular morphogenesis to stabilization.

scholarly journals Endothelial Cell-Pericyte Interactions Stimulate Basement Membrane Matrix Assembly: Influence on Vascular Tube Remodeling, Maturation, and Stabilization

2011 ◽  
Vol 18 (1) ◽  
pp. 68-80 ◽  
Author(s):  
Amber N. Stratman ◽  
George E. Davis
Keyword(s):  
Growth Factor ◽  
Basement Membrane ◽  
Basement Membranes ◽  
Heparin Binding ◽  
Matrix Assembly ◽  
Matrix Deposition ◽  
Vascular Basement Membrane ◽  
Membrane Matrix

AbstractExtracellular matrix synthesis and deposition surrounding the developing vasculature are critical for vessel remodeling and maturation events. Although the basement membrane is an integral structure underlying endothelial cells (ECs), few studies, until recently, have been performed to understand its formation in this context. In this review article, we highlight new data demonstrating a corequirement for ECs and pericytes to properly deposit and assemble vascular basement membranes during morphogenic events. In EC only cultures or under conditions whereby pericyte recruitment is blocked, there is a lack of basement membrane assembly, decreased vessel stability (with increased susceptibility to pro-regressive stimuli), and increased EC tube widths (a marker of dysfunctional EC-pericyte interactions). ECs and pericytes both contribute basement membrane components and, furthermore, both cells induce the expression of particular components as well as integrins that recognize them. The EC-derived factors—platelet derived growth factor-BB and heparin binding-epidermal growth factor—are both critical for pericyte recruitment to EC tubes and concomitant vascular basement membrane formationin vitroandin vivo. Thus, heterotypic EC-pericyte interactions play a fundamental role in vascular basement membrane matrix deposition, a critical tube maturation event that is altered in key disease states such as diabetes and cancer.

scholarly journals Endothelial-derived PDGF-BB and HB-EGF coordinately regulate pericyte recruitment during vasculogenic tube assembly and stabilization

Blood ◽  
2010 ◽  
Vol 116 (22) ◽  
pp. 4720-4730 ◽  
Author(s):  
Amber N. Stratman ◽  
Amy E. Schwindt ◽  
Kristine M. Malotte ◽  
George E. Davis
Keyword(s):  
Growth Factor ◽  
Basement Membrane ◽  
Growth Factor Receptor ◽  
Platelet Derived Growth Factor ◽  
Heparin Binding ◽  
Matrix Assembly ◽  
Matrix Deposition ◽  
Membrane Matrix

Recently, we reported a novel system whereby human pericytes are recruited to endothelial cell (EC)–lined tubes in 3-dimensional (3D) extracellular matrices to stimulate vascular maturation including basement membrane matrix assembly. Through the use of this serum-free, defined system, we demonstrate that pericyte motility within 3D collagen matrices is dependent on the copresence of ECs. Using either soluble receptor traps consisting of the extracellular ligand-binding domains of platelet-derived growth factor receptor β, epidermal growth factor receptor (EGFR), and ErbB4 receptors or blocking antibodies directed to platelet-derived growth factor (PDGF)–BB, or heparin-binding EGF-like growth factor (HB-EGF), we show that both of these EC-derived ligands are required to control pericyte motility, proliferation, and recruitment along the EC tube ablumenal surface. Blockade of pericyte recruitment causes a lack of basement membrane matrix deposition and, concomitantly, increased vessel widths. Combined inhibition of PDGF-BB and HB-EGF–induced signaling in quail embryos leads to reduced pericyte recruitment to EC tubes, decreased basement membrane matrix deposition, increased vessel widths, and vascular hemorrhage phenotypes in vivo, in support of our findings in vitro. In conclusion, we report a dual role for EC-derived PDGF-BB and HB-EGF in controlling pericyte recruitment to EC-lined tubes during developmental vascularization events.

Enhanced assembly of basement membrane matrix by endodermal cells in response to fibronectin substrata

1991 ◽  
Vol 99 (2) ◽  
pp. 443-451
Author(s):  
M.R. Austria ◽  
J.R. Couchman
Keyword(s):  
Extracellular Matrix ◽  
Basement Membrane ◽  
Basement Membranes ◽  
Binding Domain ◽  
Type I ◽  
Matrix Assembly ◽  
Matrix Deposition ◽  
Membrane Matrix ◽  
The Matrix

Basement membranes are complex extracellular matrices contributing to the regulation of growth, migration and differentiation of many cell types. However, little is known about the mechanisms regulating the deposition and assembly of basement membrane from its constituents. We have investigated the role of extracellular matrix molecules in the control of basement membrane matrix assembly by cultured endodermal (PFHR-9) cells. In the presence of fibronectin-depleted serum, substrata of fibronectin or laminin induced an increase in deposition of laminin, type IV collagen and proteoglycans by PFHR-9 cells, in comparison to cells adherent to type I collagen-coated, vitronectin-coated or uncoated substrata. Direct effects of fibronectin or laminin on the degree of cell spreading or rate of proliferation were not responsible for enhanced matrix deposition. The effect did not result from a redirection of basement membrane components to the matrix, since there was no decrease in matrix constituents released to the culture supernatants. Furthermore, the synthesis and release of other molecules that are not basement membrane constituents was unaltered in response to different extracellular matrix substrata. Experiments with fibronectin fragments showed that a 105 × 10(3) Mr ‘cell’-binding domain (containing the cell attachment sequence Arg-Gly-Asp-Ser) was an important contributor to enhanced matrix deposition, while the N-terminal 29 × 10(3) Mr heparin-binding domain also contributed to the effect, particularly with respect to heparan sulfate proteoglycan deposition. It seems that fibronectin has a dual role of action in promoting basement membrane matrix assembly, through direct cell surface interactions, and through the binding of fibronectin to other matrix components that may nucleate or stabilize the matrix assembly.

scholarly journals Type IV collagen immunoreactivity of basement membrane in inflammatory-regenerative and dysplastic lesions of the flat colonic mucosa

2003 ◽  
Vol 3 (1) ◽  
pp. 30-35
Author(s):  
Svjetlana Radović ◽  
Ivan Selak ◽  
Mirsad Babić ◽  
Željka Knežević ◽  
Zora Vukobrat-Bijedić
Keyword(s):  
Basement Membrane ◽  
Colon Adenocarcinoma ◽  
Normal Mucosa ◽  
Collagen Iv ◽  
Epithelial Dysplasia ◽  
Collagen Type Iv ◽  
Severe Dysplasia ◽  
Colon Mucosa ◽  
Mild Dysplasia ◽  
Type Iv

The aim of this research is to establish by immunohistochemistry if there is a change in the expression of collagen type IV, as a substitute of basement membrane, in development of epithelial dysplasia in chronically inflamed colon mucosa.Methods. Biopsy specimens from 270 patients were examined: 74 were classified as inflammatory-regenerative and 196 as dysplastic lesions. There were 108 cases of mild dysplasia, 58 cases of moderate and 30 cases severe dysplasia, respectively. Visualisation of collagen IV and its way of expression within basement membrane of glandular crypts was performed by immunohistochemistry and then compared with findings in normal colon mucosa and colon adenocarcinoma tissue.Results. Changes in the expression of collagen IV comprised of its focal irregularities, diffuse thinning and/or thickening, focal interruptions or its complete absence. Significant changes in the expression of collagen IV in relation to normal mucosa already occur in inflammatory-regenerative mucosa. In mild dysplasia, these changes are more intensive in relation to those in inflammatory altered mucosa as well as at severe dysplasia in relation to moderate dysplasia. Changes in the expression of collagen IV in severe dysplasia are significantly more serious than in moderate dysplasia but are identical to those in colon adenocarcinoma tissue.Conclusion. These findings suggest that change in the expression of collagen IV is in correlation to a degree of epithelial dysplasia that developed in flat chronically inflamed colon mucosa.

scholarly journals Possible Implication of Intermolecular Epitope Spreading in the Production of Anti-Glomerular Basement Membrane Antibody in Anti-Neutrophil Cytoplasmic Antibody-associated Vasculitis

2021 ◽  
Author(s):  
Yuka Nishibata ◽  
Mayu Nonokawa ◽  
Yuto Tamura ◽  
Rio Higashi ◽  
Ku Suzuki ◽  
...  
Keyword(s):  
Basement Membrane ◽  
Glomerular Basement Membrane ◽  
Immunofluorescent Staining ◽  
Enzyme Linked Immunosorbent Assay ◽  
Collagen Type Iv ◽  
Normal Kidney ◽  
Type Iv ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Α3 Subunit

Abstract ObjectiveAnti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is sometimes complicated by anti-glomerular basement membrane (GBM) disease. Proteases, including elastase, released from neutrophils activated by ANCA are implicated in the pathogenesis of AAV. Epitopes of anti-GBM antibody exist in the α3-subunit non-collagenous (NC1) domain of collagen type IV [Col (IV)]. This region, called α3(IV)NC1, is structurally cryptic. This study aimed to determine the production mechanism of anti-GBM antibody in AAV.MethodsWe first examined whether α3(IV)NC1 could be revealed by the digestion of formalin-fixed, paraffin-embedded (FFPE) normal kidney sections and Col (IV) by proteases, including neutrophil elastase, using immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA). Next, the reveal of α3(IV)NC1 and the infiltration of CD11c+ macrophages in the affected kidneys were evaluated by IHC and immunofluorescent staining using FFPE sections. Finally, the production of anti-GBM antibody in AAV rats was determined by ELISA.Resultsα3(IV)NC1 was revealed by the digestion of FFPE normal kidney sections and Col (IV) by proteases. Although the reveal of α3(IV)NC1 was observed in sclerotic glomeruli regardless of causative diseases, CD11c+ macrophages near α3(IV)NC1 were characteristics of AAV. Anti-GBM antibody was produced subsequent to ANCA in some AAV rats. IHC demonstrated the reveal of α3(IV)NC1 in affected renal tissues and the infiltration of CD11c+ macrophages around the sites.ConclusionThe collective findings suggest that, in AAV, proteases released from neutrophils activated by ANCA digest Col (IV) and result in the reveal of α3(IV)NC1, CD11c+ macrophages present GBM epitopes, and then the host’s immune system produce anti-GBM antibody.

Specific ablation of the nidogen-binding site in the laminin γ1 chain interferes with kidney and lung development

Development ◽  
2002 ◽  
Vol 129 (11) ◽  
pp. 2711-2722 ◽  
Author(s):  
Michael Willem ◽  
Nicolai Miosge ◽  
Willi Halfter ◽  
Neil Smyth ◽  
Iris Jannetti ◽  
...  
Keyword(s):  
Basement Membrane ◽  
Binding Site ◽  
Lung Development ◽  
Collagen Type Iv ◽  
Developmental Defects ◽  
Type Iv ◽  
And Function ◽  
Kidney Morphogenesis ◽  
Nidogen 1

Basement membrane assembly is of crucial importance in the development and function of tissues and during embryogenesis. Nidogen 1 was thought to be central in the assembly processes, connecting the networks formed by collagen type IV and laminins, however, targeted inactivation of nidogen 1 resulted in no obvious phenotype. We have now selectively deleted the sequence coding for the 56 amino acid nidogen-binding site, γ1III4, within the Lamc1 gene by gene targeting. Here, we show that mice homozygous for the deletion die immediately after birth, showing renal agenesis and impaired lung development. These developmental defects were attributed to locally restricted ruptures in the basement membrane of the elongating Wolffian duct and of alveolar sacculi. These data demonstrate that an interaction between two basement membrane proteins is required for early kidney morphogenesis in vivo.

Sign in / Sign up

Export Citation Format

Share Document