Regulation of Capillary Morphogenesis by the Adhesive and Mechanical Microenvironment

2011 ◽  
pp. 180-207
Keyword(s):  
Capillary Morphogenesis ◽  
Mechanical Microenvironment

Attenuation of retinal endothelial cell migration and capillary morphogenesis in the absence of bcl-2

2008 ◽  
Vol 294 (6) ◽  
pp. C1521-C1530 ◽  
Author(s):  
Shuji Kondo ◽  
Yixin Tang ◽  
Elizabeth A. Scheef ◽  
Nader Sheibani ◽  
Christine M. Sorenson
Keyword(s):  
Cell Migration ◽  
Vascular System ◽  
Ex Vivo ◽  
Vascular Development ◽  
Critical Role ◽  
Endothelial Cell Migration ◽  
Cellular Functions ◽  
Capillary Morphogenesis ◽  
Angiogenesis Assay ◽  
Ischemic Retinopathy

Apoptosis plays a critical role during development and in the maintenance of the vascular system. B-cell leukemia lymphoma 2 (bcl-2) protects endothelial cells (EC) from apoptosis in response to a variety of stimuli. Previous work from this laboratory demonstrated attenuation of postnatal retinal vascular development and retinal neovascularization during oxygen-induced ischemic retinopathy in bcl-2-deficient (bcl-2−/−) mice. To gain further insight into the function of bcl-2 in the endothelium, we isolated retinal EC from bcl-2+/+ and bcl-2−/− mice. Retinal EC lacking bcl-2 demonstrated reduced cell migration, tenascin-C expression, and adhesion to vitronectin and fibronectin. The bcl-2−/− retinal EC also failed to undergo capillary morphogenesis in Matrigel. In addition, using an ex vivo angiogenesis assay, we observed reduced sprouting from aortic rings grown in culture from bcl-2−/− mice compared with bcl-2+/+ mice. Furthermore, reexpression of bcl-2 was sufficient to restore migration and capillary morphogenesis defects observed in bcl-2−/− retinal EC. Mechanistically, bcl-2−/− cells expressed significantly less endothelial nitric oxide synthase, an important downstream effecter of proangiogenic signaling. This may be attributed to increased oxidative stress in the absence of bcl-2. In fact, incubation of retinal EC or aortic rings from bcl-2−/− mice with the antioxidant N-acetylcysteine rescued their capillary morphogenesis and sprouting defects. Thus, bcl-2-mediated cellular functions play important roles not only in survival but also in proangiogenic phenotype of EC with a significant impact on vascular development and angiogenesis.

scholarly journals O1 Elevated expression level of capillary morphogenesis gene 2 in pancreatic ductal adenocarcinoma cell is associated with distant metastasis and poor prognosis

2021 ◽  
Vol 108 (Supplement_5) ◽  
Author(s):  
Ziqian Fang ◽  
Paul Griffiths ◽  
Bilal Al-Sarireh ◽  
Wen G Jiang ◽  
Lin Ye
Keyword(s):  
Pancreatic Cancer ◽  
Tissue Microarray ◽  
Distant Metastasis ◽  
Cell Monolayer ◽  
Gene Array ◽  
Mesothelial Cell ◽  
Ductal Adenocarcinoma ◽  
Cancer Tissue ◽  
Capillary Morphogenesis ◽  
Elevated Expression

Abstract Introduction Emerging evidence revealed the active role played by capillary morphogenesis gene 2 (CMG2) during the disease progression and metastasis of some cancers. It was shown that CMG2 was increased in pancreatic tumours in our previous research. The current study further validated this finding for the expression of CMG2 in pancreatic cancer and also dissected its clinical implication. Method Immunochemical staining of CMG2 was performed on a pancreatic cancer tissue microarray (PA2081, Biomax, n = 104). Clinical relevance of CMG2 was analysed in TCGA pancreatic cancer cohort and gene array data (GSE71729) using ANOVA and Kaplan-Meier analyses. Influence of CMG2 on adhesion to a mesothelial cell monolayer was determined using both Mia-PaCa-2 and PANC-1 cell lines with CMG2 knockdown. Result CMG2 is increased significantly in pancreatic ductal adenomas, P < 0.001 compared with adjacent non-tumour tissues. Higher levels of CMG2 were also revealed in the distant metastases of pancreatic cancer, P < 0.001 compared with both primary tumuors and distant metastasis. Elevated expression CMG2 protein in pancreatic cancers was also observed on the tissue microarray. Patients with higher CMG2 expression tumours had shorter overall survival (median = 15.8 months), P < 0.001 compared with those patients with lower CMG2 expressing tumours (median = 30.4 months). Knockdown of the CMG2 significantly decreased the number of cells which adhere to the mesothelial cells (P < 0.001). Conclusion Elevated CMG2 expression in pancreatic ductal adenocarcinomas is associated with distant metastasis and shorter survival which requires further investigation to shed light on its therapeutic potential. Take-home Message Elevated CMG2 expression in pancreatic ductal adenocarcinomas is associated with distant metastasis and shorter survival.

scholarly journals Erratum: A role for sialyl Lewis-X/A glycoconjugates in capillary morphogenesis

Nature ◽  
1993 ◽  
Vol 366 (6453) ◽  
pp. 368-368
Author(s):  
Mai Nguyen ◽  
Naomi A. Strubel ◽  
Joyce Bischoff
Keyword(s):  
Sialyl Lewis X ◽  
Lewis X ◽  
Capillary Morphogenesis ◽  
Sialyl Lewis

MULTI-SCALE MECHANICAL BEHAVIOR ANALYSIS ON FLUID–SOLID COUPLING FOR OSTEONS IN VARIOUS GRAVITATIONAL FIELDS

2021 ◽  
Author(s):  
HAO ZHANG ◽  
HAI-YING LIU ◽  
CHUN-QIU ZHANG ◽  
ZHEN-ZHONG LIU ◽  
WEI WANG
Keyword(s):  
Gravitational Field ◽  
Fluid Shear Stress ◽  
Bone Matrix ◽  
Fluid Pressure ◽  
Gravity Gradient ◽  
Static Compression ◽  
Gravitational Fields ◽  
Multi Scale ◽  
Earth’S Gravitational Field ◽  
Mechanical Microenvironment

Background: Compact bone mainly consists of cylindrical osteon structures. In microgravity, the change in the mechanical microenvironment of osteocytes might be the root cause of astronauts’ bone loss during space flights. Methods: A multi-scale three-dimensional (3D) fluid–solid coupling finite element model of osteons with a two-stage pore structure was developed using COMSOL software based on the natural structure of osteocytes. Gradients in gravitational fields of [Formula: see text]1, 0, 1, 2.5, and 3.7[Formula: see text]g were used to investigate the changes in the mechanical microenvironment on osteocyte structure. The difference in arteriole pulsating pressure and static compression stress caused by each gravity gradient was investigated. Results: The mechanical response of osteocytes increased with the value of g, compared with the Earth’s gravitational field. For instance, the fluid pressure of osteocytes and the von Mises stress of bone matrix near lacunae decreased by 31.3% and 99.9%, respectively, in microgravity. Under static loading, only about 16.7% of osteocytes in microgravity and 58.3% of osteocytes in the Earth’s gravitational field could reach the fluid shear stress threshold of biological reactions in cell culture experiments. Compared with the Earth’s gravitational field, the pressure gradient inside osteocytes severely decreased in microgravity. Conclusion: The mechanical microenvironment of osteocytes in microgravity might cause significant changes in the mechanical microenvironment of osteocytes, which may lead to disuse osteoporosis in astronauts.

scholarly journals Binding of the von Willebrand Factor A Domain of Capillary Morphogenesis Protein 2 to Anthrax Protective Antigen Vaccine Reduces Immunogenicity in Mice

mSphere ◽  
2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Fabiana Freire Mendes de Oliveira ◽  
Sireesha Mamillapalli ◽  
Srinivas Gonti ◽  
Robert N. Brey ◽  
Han Li ◽  
...  
Keyword(s):  
Immune Response ◽  
Von Willebrand Factor ◽  
Neutralizing Antibodies ◽  
Protective Antigen ◽  
Antibody Responses ◽  
Anthrax Toxin ◽  
Anthrax Vaccine ◽  
Capillary Morphogenesis ◽  
Von Willebrand ◽  
Willebrand Factor

ABSTRACT Protective antigen (PA) is a component of anthrax toxin that can elicit toxin-neutralizing antibody responses. PA is also the major antigen in the current vaccine to prevent anthrax, but stability problems with recombinant proteins have complicated the development of new vaccines containing recombinant PA. The relationship between antigen physical stability and immunogenicity is poorly understood, but there are theoretical reasons to think that this parameter can affect immune responses. We investigated the immunogenicity of anthrax PA, in the presence and absence of the soluble von Willebrand factor A domain of the human form of receptor capillary morphogenesis protein 2 (sCMG2), to elicit antibodies to PA in BALB/c mice. Prior studies showed that sCMG2 stabilizes the 83-kDa PA structure to pH, chemical denaturants, temperature, and proteolysis and slows the hydrogen-deuterium exchange rate of histidine residues far from the binding interface. In contrast to a vaccine containing PA without adjuvant, we found that mice immunized with PA in stable complex with sCMG2 showed markedly reduced antibody responses to PA, including toxin-neutralizing antibodies and antibodies to domain 4, which correlated with fewer toxin-neutralizing antibodies. In contrast, mice immunized with PA in concert with a nonbinding mutant of sCMG2 (D50A) showed anti-PA antibody responses similar to those observed with PA alone. Our results suggest that addition of sCMG2 to a PA vaccine formulation is likely to result in a significantly diminished immune response, but we discuss the multitude of factors that could contribute to reduced immunogenicity. IMPORTANCE The anthrax toxin PA is the major immunogen in the current anthrax vaccine (anthrax vaccine adsorbed). Improving the anthrax vaccine for avoidance of a cold chain necessitates improvements in the thermodynamic stability of PA. We address how stabilizing PA using sCMG2 affects PA immunogenicity in BALB/c mice. Although the stability of PA is increased by binding to sCMG2, PA immunogenicity is decreased. This study emphasizes that, while binding of a ligand retains or improves conformational stability without affecting the native sequence, epitope recognition or processing may be affected, abrogating an effective immune response.

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