scholarly journals Thalidomide Suppresses Angiogenesis Through the Signal Transducer and Activator of Transcription 3/SP4 Signaling Pathway in the Peritoneal Membrane

2021 ◽  
Vol 12 ◽  
Author(s):  
Nan Zhu ◽  
Ling Wang ◽  
Huimin Guo ◽  
Jieshuang Jia ◽  
Lijie Gu ◽  
...  
Keyword(s):  
Tube Formation ◽  
Signal Transducer ◽  
Peritoneal Membrane ◽  
Peritoneal Mesothelial Cells ◽  
Endothelial Tube Formation ◽  
Vascular Proliferation ◽  
Human Peritoneal Mesothelial Cells ◽  
Endothelial Growth Factor ◽  
Transcription 3

Peritoneal angiogenesis is the key pathophysiological factor that limits peritoneal ultrafiltration during peritoneal dialysis (PD) in uremic patients. Thalidomide has been confirmed to inhibit angiogenesis by inhibiting the secretion of vascular endothelial growth factor (VEGF), but the exact mechanism by which thalidomide inhibits vascular proliferation during PD is still unclear. Here, the objective of the present study was to investigate whether the reduction in VEGF production by human peritoneal mesothelial cells (HPMCs) was controlled by thalidomide. Stimulation of HPMCs with IL-6 in combination with soluble IL-6 receptor (sIL-6R) promoted VEGF expression and secretion, but these effects were attenuated by thalidomide treatment through a transcriptional mechanism that involved signal transducer and activator of transcription 3 (STAT3) and SP4. Conditioned medium from HPMCs cultured with thalidomide inhibited angiogenic endothelial tube formation, which could be further blocked by silencing SP4 and promoted by overexpressing SP4. In vivo, induction of peritoneal angiogenesis in sham rats, sham+PD rats, 5/6 nephrectomy (5/6Nx) rats, 5/6Nx+PD rats, and 5/6Nx+PD rats intraperitoneally treated with thalidomide showed that thalidomide was involved in the control of several key endothelial–specific targets, including VEGFR2, VEGFR3, SP4, and STAT3 expression and new vessel formation, confirming the role of thalidomide and STAT3/SP4 signaling in these processes. Taken together, these findings identify a novel mechanism that links thalidomide, STAT3/SP4 signaling, and angiogenesis in the peritoneal membrane.

The recombinant lectin-like domain of thrombomodulin inhibits angiogenesis through interaction with Lewis Y antigen

Blood ◽  
2012 ◽  
Vol 119 (5) ◽  
pp. 1302-1313 ◽  
Author(s):  
Cheng-Hsiang Kuo ◽  
Po-Ku Chen ◽  
Bi-Ing Chang ◽  
Meng-Chen Sung ◽  
Chung-Sheng Shi ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Egf Receptor ◽  
Tube Formation ◽  
Endothelial Tube Formation ◽  
A Cell ◽  
Lewis Y ◽  
Tm Domain

AbstractLewis Y Ag (LeY) is a cell-surface tetrasaccharide that participates in angiogenesis. Recently, we demonstrated that LeY is a specific ligand of the recombinant lectin-like domain of thrombomodulin (TM). However, the biologic function of interaction between LeY and TM in endothelial cells has never been investigated. Therefore, the role of LeY in tube formation and the role of the recombinant lectin-like domain of TM—TM domain 1 (rTMD1)—in antiangiogenesis were investigated. The recombinant TM ectodomain exhibited lower angiogenic activity than did the recombinant TM domains 2 and 3. rTMD1 interacted with soluble LeY and membrane-bound LeY and inhibited soluble LeY-mediated chemotaxis of endothelial cells. LeY was highly expressed on membrane ruffles and protrusions during tube formation on Matrigel. Blockade of LeY with rTMD1 or Ab against LeY inhibited endothelial tube formation in vitro. Epidermal growth factor (EGF) receptor in HUVECs was LeY modified. rTMD1 inhibited EGF receptor signaling, chemotaxis, and tube formation in vitro, and EGF-mediated angiogenesis and tumor angiogenesis in vivo. We concluded that LeY is involved in vascular endothelial tube formation and rTMD1 inhibits angiogenesis via interaction with LeY. Administration of rTMD1 or recombinant adeno-associated virus vector carrying TMD1 could be a promising antiangiogenesis strategy.

scholarly journals Cardioprotective Activity of Selected Polyphenols Based on Epithelial and Aortic Cell Lines. A Review

Molecules ◽  
2020 ◽  
Vol 25 (22) ◽  
pp. 5343
Author(s):  
Michał Otręba ◽  
Leon Kośmider ◽  
Jerzy Stojko ◽  
Anna Rzepecka-Stojko
Keyword(s):  
Endothelial Cells ◽  
Tube Formation ◽  
Health Claims ◽  
In Vivo Studies ◽  
Positive Effects ◽  
Endothelial Tube Formation ◽  
Disease Therapy ◽  
Species Production

Polyphenols have recently gained popularity among the general public as products and diets classified as healthy and containing naturally occurring phenols. Many polyphenolic extracts are available on the market as dietary supplements, functional foods, or cosmetics, taking advantage of clients’ desire to live a healthier and longer life. However, due to the difficulty of discovering the in vivo functions of polyphenols, most of the research focuses on in vitro studies. In this review, we focused on the cardioprotective activity of different polyphenols as possible candidates for use in cardiovascular disease therapy and for improving the quality of life of patients. Thus, the studies, which were mainly based on endothelial cells, aortic cells, and some in vivo studies, were analyzed. Based on the reviewed articles, polyphenols have a few points of action, including inhibition of acetylcholinesterase, decrease in reactive oxygen species production and endothelial tube formation, stimulation of acetylcholine-induced endothelium-derived mediator release, and others, which lead to their cardio- and/or vasoprotective effects on endothelial cells. The obtained results suggest positive effects of polyphenols, but more long-term in vivo studies demonstrating effects on mechanism of action, sensitivity, and specificity or efficacy are needed before legal health claims can be made.

scholarly journals Helicobacter pylori Cytotoxin-Associated Gene A Activates the Signal Transducer and Activator of Transcription 3 Pathway In vitro and In vivo

2009 ◽  
Vol 69 (2) ◽  
pp. 632-639 ◽  
Author(s):  
Dana M. Bronte-Tinkew ◽  
Mauricio Terebiznik ◽  
Aime Franco ◽  
Michelle Ang ◽  
Diane Ahn ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Signal Transducer ◽  
Cytotoxin Associated Gene A ◽  
Transcription 3

scholarly journals Stromal cell–derived factor 1 promotes angiogenesis via a heme oxygenase 1–dependent mechanism

2007 ◽  
Vol 204 (3) ◽  
pp. 605-618 ◽  
Author(s):  
Jessy Deshane ◽  
Sifeng Chen ◽  
Sergio Caballero ◽  
Anna Grochot-Przeczek ◽  
Halina Was ◽  
...  
Keyword(s):  
Wound Healing ◽  
Heme Oxygenase ◽  
Stromal Cell ◽  
Tube Formation ◽  
Heme Oxygenase 1 ◽  
Impaired Wound Healing ◽  
Endothelial Tube Formation ◽  
Stromal Cell Derived Factor ◽  
And Migration

Stromal cell–derived factor 1 (SDF-1) plays a major role in the migration, recruitment, and retention of endothelial progenitor cells to sites of ischemic injury and contributes to neovascularization. We provide direct evidence demonstrating an important role for heme oxygenase 1 (HO-1) in mediating the proangiogenic effects of SDF-1. Nanomolar concentrations of SDF-1 induced HO-1 in endothelial cells through a protein kinase C ζ–dependent and vascular endothelial growth factor–independent mechanism. SDF-1–induced endothelial tube formation and migration was impaired in HO-1–deficient cells. Aortic rings from HO-1−/− mice were unable to form capillary sprouts in response to SDF-1, a defect reversed by CO, a byproduct of the HO-1 reaction. Phosphorylation of vasodilator-stimulated phosphoprotein was impaired in HO-1−/− cells, an event that was restored by CO. The functional significance of HO-1 in the proangiogenic effects of SDF-1 was confirmed in Matrigel plug, wound healing, and retinal ischemia models in vivo. The absence of HO-1 was associated with impaired wound healing. Intravitreal adoptive transfer of HO-1–deficient endothelial precursors showed defective homing and reendothelialization of the retinal vasculature compared with HO-1 wild-type cells following ischemia. These findings demonstrate a mechanistic role for HO-1 in SDF-1–mediated angiogenesis and provide new avenues for therapeutic approaches in vascular repair.

scholarly journals Regulation of Synthesis and Roles of Hyaluronan in Peritoneal Dialysis

2015 ◽  
Vol 2015 ◽  
pp. 1-12
Author(s):  
Timothy Bowen ◽  
Soma Meran ◽  
Aled P. Williams ◽  
Lucy J. Newbury ◽  
Matthias Sauter ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
In Vivo Models ◽  
Peritoneal Mesothelial Cells ◽  
Glycosidic Bonds ◽  
Peritoneal Biopsy ◽  
Human Peritoneal Mesothelial Cells ◽  
Regulation Of Synthesis ◽  
Ha Synthase

Hyaluronan (HA) is a ubiquitous extracellular matrix glycosaminoglycan composed of repeated disaccharide units of alternating D-glucuronic acid and D-N-acetylglucosamine residues linked via alternatingβ-1,4 andβ-1,3 glycosidic bonds. HA is synthesized in humans by HA synthase (HAS) enzymes 1, 2, and 3, which are encoded by the correspondingHASgenes. Previous in vitro studies have shown characteristic changes in HAS expression and increased HA synthesis in response to wounding and proinflammatory cytokines in human peritoneal mesothelial cells. In addition, in vivo models and human peritoneal biopsy samples have provided evidence of changes in HA metabolism in the fibrosis that at present accompanies peritoneal dialysis treatment. This review discusses these published observations and how they might contribute to improvement in peritoneal dialysis.

scholarly journals Astaxanthin Ameliorates Lipopolysaccharide-Induced Neuroinflammation, Oxidative Stress and Memory Dysfunction through Inactivation of the Signal Transducer and Activator of Transcription 3 Pathway

Marine Drugs ◽  
2019 ◽  
Vol 17 (2) ◽  
pp. 123 ◽  
Author(s):  
Ji Han ◽  
Yong Lee ◽  
Jun Im ◽  
Young Ham ◽  
Hee Lee ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Binding ◽  
Inflammatory Responses ◽  
Memory Loss ◽  
Signal Transducer ◽  
Mice Model ◽  
Neuroinflammatory Response ◽  
Transcription 3

Astaxanthin (AXT), a xanthophyll carotenoid compound, has potent antioxidant, anti-inflammatory and neuroprotective properties. Neuroinflammation and oxidative stress are significant in the pathogenesis and development of Alzheimer’s disease (AD). Here, we studied whether AXT could alleviate neuroinflammation, oxidative stress and memory loss in lipopolysaccharide (LPS) administered mice model. Additionally, we investigated the anti-oxidant activity and the anti-neuroinflammatory response of AXT in LPS-treated BV-2 microglial cells. The AXT administration ameliorated LPS-induced memory loss. This effect was associated with the reduction of LPS-induced expression of inflammatory proteins, as well as the production of reactive oxygen species (ROS), nitric oxide (NO), cytokines and chemokines both in vivo and in vitro. AXT also reduced LPS-induced β-secretase and Aβ1–42 generation through the down-regulation of amyloidogenic proteins both in vivo and in vitro. Furthermore, AXT suppressed the DNA binding activities of the signal transducer and activator of transcription 3 (STAT3). We found that AXT directly bound to the DNA- binding domain (DBD) and linker domain (LD) domains of STAT3 using docking studies. The oxidative stress and inflammatory responses were not downregulated in BV-2 cells transfected with DBD-null STAT3 and LD-null STAT3. These results indicated AXT inhibits LPS-induced oxidant activity, neuroinflammatory response and amyloidogenesis via the blocking of STAT3 activity through direct binding.

scholarly journals Exosomal miR-135b shed from hypoxic multiple myeloma cells enhances angiogenesis by targeting factor-inhibiting HIF-1

Blood ◽  
2014 ◽  
Vol 124 (25) ◽  
pp. 3748-3757 ◽  
Author(s):  
Tomohiro Umezu ◽  
Hiroko Tadokoro ◽  
Kenko Azuma ◽  
Seiichiro Yoshizawa ◽  
Kazuma Ohyashiki ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Tube Formation ◽  
Myeloma Cells ◽  
Endothelial Tube Formation ◽  
Key Points ◽  
Resistant Cells

Key Points We established hypoxia-resistant cells that can mimic in vivo conditions of hypoxic bone marrow. Exosomal miR-135b derived from these cell lines enhanced endothelial tube formation under hypoxia via the HIF-FIH signaling pathway.

scholarly journals Splicing factor hnRNPA2B1 contributes to tumorigenic potential of breast cancer cells through STAT3 and ERK1/2 signaling pathway

Tumor Biology ◽  
2017 ◽  
Vol 39 (3) ◽  
pp. 101042831769431 ◽  
Author(s):  
Ying Hu ◽  
Zihan Sun ◽  
Jinmu Deng ◽  
Baoquan Hu ◽  
Wenting Yan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Signal Transducer ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Tumorigenic Potential ◽  
Transcription 3

Increasing evidence has indicated that the splicing factor hnRNPA2B1 plays a direct role in cancer development, progression, gene expression, and signal transduction. Previous studies have shown that knocking down hnRNPA2B1 in breast cancer cells induces apoptosis, but the mechanism and other functions of hnRNPA2B1 in breast cancer are unknown. The goal of this study was to investigate the biological function, clinical significance, and mechanism of hnRNPA2B1 in breast cancer. The expression of hnRNPA2B1 in 92 breast cancer and adjacent normal tissue pairs was analyzed by immunohistochemical staining. Stable clones exhibiting knockdown of hnRNPA2B1 via small hairpin RNA expression were generated using RNA interference technology in breast cancer cell lines. The effects of hnRNPA2B1 on cell proliferation were examined by MTT and EdU assay, and cellular apoptosis and the cell cycle were examined by flow cytometry. A nude mouse xenograft model was established to elucidate the function of hnRNPA2B1 in tumorigenesis in vivo. The role of hnRNPA2B1 in signaling pathways was investigated in vitro. Our data revealed that hnRNPA2B1 was overexpressed in breast cancer tissue specimens and cell lines. Knockdown of hnRNPA2B1 reduced breast cancer cell proliferation, induced apoptosis, and prolonged the S phase of the cell cycle in vitro. In addition, hnRNPA2B1 knockdown suppressed subcutaneous tumorigenicity in vivo. On a molecular level, hnRNPA2B1 knockdown decreased signal transducer and activator of transcription 3 and extracellular-signal-regulated kinase 1/2 phosphorylation. We concluded that hnRNPA2B1 promotes the tumorigenic potential of breast cancer cells, MCF-7 and MDA-MB-231, through the extracellular-signal-regulated kinase 1/2 or signal transducer and activator of transcription 3 pathway, which may serve as a target for future therapies.

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