scholarly journals Blood–Nerve Barrier (BNB) Pathology in Diabetic Peripheral Neuropathy and In Vitro Human BNB Model

2020 ◽  
Vol 22 (1) ◽  
pp. 62
Author(s):  
Yukio Takeshita ◽  
Ryota Sato ◽  
Takashi Kanda
Keyword(s):  
Endothelial Cells ◽  
Peripheral Neuropathy ◽  
Schwann Cells ◽  
Cell Lines ◽  
Diabetic Peripheral Neuropathy ◽  
Peripheral Nerves ◽  
Vascular Endothelial Cells ◽  
Vascular Endothelial ◽  
Immortalized Cell

In diabetic peripheral neuropathy (DPN), metabolic disorder by hyperglycemia progresses in peripheral nerves. In addition to the direct damage to peripheral neural axons, the homeostatic mechanism of peripheral nerves is disrupted by dysfunction of the blood–nerve barrier (BNB) and Schwann cells. The disruption of the BNB, which is a crucial factor in DPN development and exacerbation, causes axonal degeneration via various pathways. Although many reports revealed that hyperglycemia and other important factors, such as dyslipidemia-induced dysfunction of Schwann cells, contributed to DPN, the molecular mechanisms underlying BNB disruption have not been sufficiently elucidated, mainly because of the lack of in vitro studies owing to difficulties in establishing human cell lines from vascular endothelial cells and pericytes that form the BNB. We have developed, for the first time, temperature-sensitive immortalized cell lines of vascular endothelial cells and pericytes originating from the BNB of human sciatic nerves, and we have elucidated the disruption to the BNB mainly in response to advanced glycation end products in DPN. Recently, we succeeded in developing an in vitro BNB model to reflect the anatomical characteristics of the BNB using cell sheet engineering, and we established immortalized cell lines originating from the human BNB. In this article, we review the pathologic evidence of the pathology of DPN in terms of BNB disruption, and we introduce the current in vitro BNB models.

scholarly journals Cancer Exosome-derived Integrin α6 and Integrin β4 Promote Lung Metastasis of Colorectal Cancer

2020 ◽  
Author(s):  
Tao Luo ◽  
Jiahao Huang ◽  
Changtao Wu ◽  
Qinghua Huang ◽  
Huage Zhong ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Endothelial Cells ◽  
Cell Lines ◽  
Lung Metastasis ◽  
Vascular Endothelial Cells ◽  
Ectopic Expression ◽  
Vascular Endothelial ◽  
Integrin Β4

Abstract Background: Colorectal cancer (CRC) metastasis remains the major cause of the CRC mortality, while the underlying mechanisms remain to be fully understood. In this study we investigated the role of cancer exosomes in CRC lung metastasis in vivo and in vitro. Methods: Expressions of Integrinα6 and Integrin β4 were examined in CRC cells as well as released exosomes. Co-culture assay with vascular endothelial cells was also analyzed.Results: We found that Integrin α6 and Integrin β4 are overexpressed in highly tumorigenic and metastatic CRC cell lines HCT116 and SW620 and their secreted exosomes, compared to the low tumorigenic and non-metastatic CRC cell lines. Disruption of ITGA6 and ITGB4 expression in CRC decreased the proliferation and tubulogenic capacities of vascular endothelial cells significantly, while ectopic expression of ITGA6 and ITGB4 gave rise to opposite effects. Further more, we demonstrated that exosomal ITGA6 and ITGB4 promoted the lung metastasis of CRCs in vivo.Conclusions: Our study provides new insight into the molecular mechanism of CRC metastasis by which CRC-derived exosomal ITGA6 and ITGB4 induce organotropism to the lung, leading to increased tubulogenic capacity and metastasis. It also reveals a biomarker-based prediction for CRC metastasis and a novel potential therapeutic targets for CRC.

scholarly journals The Use of Fiber-Reinforced Scaffolds Cocultured with Schwann Cells and Vascular Endothelial Cells to Repair Rabbit Sciatic Nerve Defect with Vascularization

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Hongyang Gao ◽  
Yang You ◽  
Guoping Zhang ◽  
Feng Zhao ◽  
Ziyi Sha ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Sciatic Nerve ◽  
Nerve Fiber ◽  
Schwann Cells ◽  
Vascular Endothelial Cells ◽  
Neurological Function ◽  
Control Group ◽  
Vascular Endothelial ◽  
Fiber Reinforced ◽  
3D Scaffolds

To explore the feasibility of biodegradable fiber-reinforced 3D scaffolds with satisfactory mechanical properties for the repair of long-distance sciatic nerve defect in rabbits and effects of vascularized graft in early stage on the recovery of neurological function, Schwann cells and vascular endothelial cells were cocultured in the fiber-reinforced 3D scaffolds. Experiment group which used prevascularized nerve complex for the repair of sciatic nerve defect and control group which only cultured with Schwann cells were set. The animals in both groups underwent electromyography to show the status of the neurological function recovery at 4, 8, and 16 weeks after the surgery. Sciatic nerve regeneration and myelination were observed under the light microscope and electron microscope. Myelin sheath thickness, axonal diameter, and number of myelinated nerve fiber were quantitatively analyzed using image analysis system. The recovery of foot ulcer, the velocity of nerve conduction, the number of regenerating nerve fiber, and the recovery of ultrastructure were increased in the experimental group than those in the control group. Prevascularized tissue engineered fiber-reinforced 3D scaffolds for the repair of sciatic nerve defects in rabbits can effectively promote the recovery of neurological function.

scholarly journals Synthesis and physiological activity of heterodimers comprising different splice forms of vascular endothelial growth factor and placenta growth factor

1996 ◽  
Vol 316 (3) ◽  
pp. 703-707 ◽  
Author(s):  
Ralf BIRKENHÄGER ◽  
Bernard SCHNEPPE ◽  
Wolfgang RÖCKL ◽  
Jörg WILTING ◽  
Herbert A. WEICH ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Vascular Endothelial Cells ◽  
Physiological Activity ◽  
Expression System ◽  
Vascular Endothelial ◽  
Placenta Growth Factor ◽  
Splice Forms

Vascular endothilial growth factor (VEGF) and placenta growth factor (PIGF) are members of a dimeric-growth-factor family with angiogenic properties. VEGF is a highly potent and specific mitogen for endothelial cells, playing a vital role in angiogenesis in vivo. The role of PIGF is less clear. We expressed the monomeric splice forms VEGF-165, VEGF-121, PIGF-1 and PlGF-2 as unfused genes in Escherichia coli using the pCYTEXP expression system. In vitro dimerization experiments revealed that both homo- and hetero-dimers can be formed from these monomeric proteins. The dimers were tested for their ability to promote capillary growth in vivo and stimulate DNA synthesis in cultured human vascular endothelial cells. Heterodimers comprising different VEGF splice forms, or combinations of VEGF/PlGF splice forms, showed mitogenic activity. The results demonstrate that four different heterodimeric growth factors are likely to have as yet uncharacterized functions in vivo.

scholarly journals Regulation of capillary tubules and lipid formation in vascular endothelial cells and macrophages via extracellular vesicle-mediated microRNA-4306 transfer

2018 ◽  
Vol 47 (1) ◽  
pp. 453-469 ◽  
Author(s):  
Ying Yang ◽  
Hui Luo ◽  
Can Zhou ◽  
Rongyi Zhang ◽  
Si Liu ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Coronary Artery ◽  
Vascular Endothelial Cells ◽  
Density Lipoprotein ◽  
Extracellular Vesicle ◽  
Luciferase Reporter ◽  
Vascular Endothelial ◽  
Human Coronary Artery ◽  
Lipid Formation

Objective This study aimed to examine regulation of capillary tubules and lipid formation in vascular endothelial cells and macrophages via extracellular vesicle-mediated microRNA (miRNA)-4306 transfer Methods Whole blood samples (12 mL) were collected from 53 patients, and miR-4306 levels in extracellular vesicles (EVs) were analyzed by reverse transcription-polymerase chain reaction. Human coronary artery vascular endothelial cells (HCAECs) and human monocyte-derived macrophages (HMDMs) were transfected with a scrambled oligonucleotide, an miR-4306 mimic, or an anti-miR-4306 inhibitor. The direct effect of miR-4306 on the target gene was analyzed by a dual-luciferase reporter assay. Results EV-contained miR-4306 released from HMDMs was significantly upregulated in coronary artery disease. Oxidized low-density lipoprotein (ox-LDL)-stimulated HMDM-derived EVs inhibited proliferation, migration, and angiogenesis abilities of HCAECs in vitro. However, ox-LDL-stimulated HCAEC-derived EVs enhanced lipid formation of HMDMs. The possible mechanism of these findings was partly due to EV-mediated miR-4306 upregulation of the Akt/nuclear factor kappa B signaling pathway. Conclusions Paracrine cellular crosstalk between HCAECs and HMDMs probably supports the pro-atherosclerotic effects of EVs under ox-LDL stress.

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