scholarly journals Osteopontin Promotes Trophoblast Invasion in the Smooth Muscle Cell-Endothelial Co-Culture At Least Via Targeting Integrin αvβ3

2020 ◽  
Vol 29 ◽  
pp. 096368972096597
Author(s):  
Ru Ke ◽  
Liting Zheng ◽  
Falan Zhao ◽  
Junxia Xia
Keyword(s):  
Smooth Muscle ◽  
Molecular Mechanisms ◽  
Culture Media ◽  
Integrin Αvβ3 ◽  
Trophoblast Invasion ◽  
Invasive Potential ◽  
Transwell Invasion Assay ◽  
Invasive Capacity ◽  
Underlying Mechanisms ◽  
Integrin Beta 3

Preeclampsia is a pregnancy disorder, whereas the underlying mechanisms and etiological factors of this complication remain elusive. Studies have reported that decreased invasiveness of trophoblast cells, immunity disorder in the maternal–fetal interface, and oxidative stress may contribute to the development of preeclampsia. In the present study, we firstly co-cultured the smooth muscle cells (SMCs) and endothelial cells (ECs) to mimic the decidua and myometrium interface and examined the effects of osteopontin (OPN) on the invasive potential of trophoblasts in the SMC-EC co-culturing system. Our results showed that HTR-8/SVneo cells after hypoxia treatment showed enhanced invasive potential in the SMC-EC co-culturing system. OPN levels in the culture media from hypoxia-treated HTR-8/SVneo cells were significantly increased. More importantly, OPN treatment upregulated integrin, beta 3 and integrin, beta 5 expression in HTR-8/SVneo cells, and promoted HTR-8/SVneo cell invasion in the transwell invasion assay and SMC-EC co-culturing system. Mechanistically, treatment with integrin αvβ3 inhibitor significantly attenuated the enhanced invasive potential of HTR-8/SVneo cells treated with OPN in the SMC-EC co-culturing system. In conclusion, our study for the first time established the SMC-EC co-culturing system to examine the invasive potential of trophoblasts. Our results indicated that OPN promoted the invasive capacity of trophoblasts via at least targeting αvβ3 in the EC-SMC co-culturing system. Future studies were required to further validate the EC-SMC co-culturing system and to determine the molecular mechanisms of OPN-mediated trophoblast invasion.

scholarly journals TNF-α Regulated Endometrial Stroma Secretome Promotes Trophoblast Invasion

2021 ◽  
Vol 12 ◽  
Author(s):  
Yuan You ◽  
Patrick Stelzl ◽  
Dana N. Joseph ◽  
Paulomi B. Aldo ◽  
Anthony J. Maxwell ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Embryo Implantation ◽  
Trophoblast Invasion ◽  
Migration And Invasion ◽  
Endometrial Stroma ◽  
Relative Contribution ◽  
Tnf Α ◽  
Invasive Capacity ◽  
Trophoblast Migration

Successful implantation requires the coordinated migration and invasion of trophoblast cells from out of the blastocyst and into the endometrium. This process relies on signals produced by cells in the maternal endometrium. However, the relative contribution of stroma cells remains unclear. The study of human implantation has major technical limitations, therefore the need of in vitro models to elucidate the molecular mechanisms. Using a recently described 3D in vitro models we evaluated the interaction between trophoblasts and human endometrial stroma cells (hESC), we assessed the process of trophoblast migration and invasion in the presence of stroma derived factors. We demonstrate that hESC promotes trophoblast invasion through the generation of an inflammatory environment modulated by TNF-α. We also show the role of stromal derived IL-17 as a promoter of trophoblast migration through the induction of essential genes that confer invasive capacity to cells of the trophectoderm. In conclusion, we describe the characterization of a cellular inflammatory network that may be important for blastocyst implantation. Our findings provide a new insight into the complexity of the implantation process and reveal the importance of inflammation for embryo implantation.

The Role of Ubiquitin E3 Ligase in Atherosclerosis

2020 ◽  
Vol 28 (1) ◽  
pp. 152-168
Author(s):  
Zhi-Xiang Zhou ◽  
Zhong Ren ◽  
Bin-Jie Yan ◽  
Shun-Lin Qu ◽  
Zhi-Han Tang ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Vascular Smooth Muscle Cell ◽  
Protein Modification ◽  
Molecular Mechanisms ◽  
Cholesterol Metabolism ◽  
Atherosclerotic Cardiovascular Disease ◽  
E3 Ligases

: Atherosclerosis is a chronic inflammatory vascular disease. Atherosclerotic cardiovascular disease is the main cause of death in both developed and developing countries. Many pathophysiological factors, including abnormal cholesterol metabolism, vascular inflammatory response, endothelial dysfunction and vascular smooth muscle cell proliferation and apoptosis, contribute to the development of atherosclerosis and the molecular mechanisms underlying the development of atherosclerosis are not fully understood. Ubiquitination is a multistep post-translational protein modification that participates in many important cellular processes. Emerging evidence suggests that ubiquitination plays important roles in the pathogenesis of atherosclerosis in many ways, including regulation of vascular inflammation, endothelial cell and vascular smooth muscle cell function, lipid metabolism and atherosclerotic plaque stability. This review summarizes important contributions of various E3 ligases to the development of atherosclerosis. Targeting ubiquitin E3 ligases may provide a novel strategy for the prevention of the progression of atherosclerosis.

Novel Findings of Anti-cancer Property of Propofol

2018 ◽  
Vol 18 (2) ◽  
pp. 156-165 ◽  
Author(s):  
Jiaqiang Wang ◽  
Chien-shan Cheng ◽  
Yan Lu ◽  
Xiaowei Ding ◽  
Minmin Zhu ◽  
...  
Keyword(s):  
General Anesthesia ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Intravenous Anesthetic ◽  
The Past ◽  
Anti Cancer ◽  
Underlying Mechanisms ◽  
Recent Attention

Background: Propofol, a widely used intravenous anesthetic agent, is traditionally applied for sedation and general anesthesia. Explanation: Recent attention has been drawn to explore the effect and mechanisms of propofol against cancer progression in vitro and in vivo. Specifically, the proliferation-inhibiting and apoptosis-inducing properties of propofol in cancer have been studied. However, the underlying mechanisms remain unclear. Conclusion: This review focused on the findings within the past ten years and aimed to provide a general overview of propofol's malignance-modulating properties and the potential molecular mechanisms.

scholarly journals Transcriptome and proteome analysis suggest enhanced photosynthesis in tetraploid Liriodendron sino-americanum

2021 ◽  
Author(s):  
Tingting Chen ◽  
Yu Sheng ◽  
Zhaodong Hao ◽  
Xiaofei Long ◽  
Fangfang Fu ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Protein Complexes ◽  
Proteome Analysis ◽  
Tree Height ◽  
Photosynthetic Electron Transport ◽  
Industrial Applications ◽  
Chlorophyll Protein Complexes ◽  
Chlorophyll Protein ◽  
Photosynthesis Genes ◽  
Underlying Mechanisms

Abstract Polyploidy generally provides an advantage in phenotypic variation and growth vigor. However, the underlying mechanisms remain poorly understood. The tetraploid L. sino-americanum exhibits altered morphology compared to its diploid counterpart, including larger, thicker and deeper green leaves, bigger stomata, thicker stems and increased tree height. Such characteristics can be useful in ornamental and industrial applications. To elucidate the molecular mechanisms behind this variation, we performed a comparative transcriptome and proteome analysis. Our transcriptome data indicated that some photosynthesis genes and pathways were differentially altered and enriched in tetraploid L. sino-americanum, mainly related to F-type ATPase, the cytochrome b6/f complex, photosynthetic electron transport, the light harvesting chlorophyll protein complexes, photosystem I and II. Most of the differentially expressed proteins we could identify are also involved in photosynthesis. Our physiological results showed that tetraploids have an enhanced photosynthetic capacity, concomitant with great levels of sugar and starch in leaves. This suggests that tetraploid L. sino-americanum might experience comprehensive transcriptome reprogramming of genes related to photosynthesis. This study has especially emphasized molecular changes involved in photosynthesis that accompany polyploidy, and provides a possible explanation for the altered phenotype of polyploidy plants in comparison to their diploid form.

scholarly journals HSP90-dependent PUS7 overexpression facilitates the metastasis of colorectal cancer cells by regulating LASP1 abundance

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Dan Song ◽  
Ming Guo ◽  
Shuai Xu ◽  
Xiaotian Song ◽  
Bin Bai ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Intellectual Development ◽  
Molecular Mechanisms ◽  
Hsp90 Inhibitor ◽  
Pseudouridine Synthase ◽  
Novel Approach ◽  
Cell Metastasis ◽  
Underlying Mechanisms

Abstract Background Pseudouridine synthase (PUS) 7 is a member of the PUS family that catalyses pseudouridine formation. It has been shown to be involved in intellectual development and haematological malignancies. Nevertheless, the role and the underlying molecular mechanisms of PUS7 in solid tumours, such as colorectal cancer (CRC), remain unexplored. This study elucidated, for the first time, the role of PUS7 in CRC cell metastasis and the underlying mechanisms. Methods We conducted immunohistochemistry, qPCR, and western blotting to quantify the expression of PUS7 in CRC tissues as well as cell lines. Besides, diverse in vivo and in vitro functional tests were employed to establish the function of PUS7 in CRC. RNA-seq and proteome profiling analysis were also applied to identify the targets of PUS7. PUS7-interacting proteins were further uncovered using immunoprecipitation and mass spectrometry. Results Overexpression of PUS7 was observed in CRC tissues and was linked to advanced clinical stages and shorter overall survival. PUS7 silencing effectively repressed CRC cell metastasis, while its upregulation promoted metastasis, independently of the PUS7 catalytic activity. LASP1 was identified as a downstream effector of PUS7. Forced LASP1 expression abolished the metastasis suppression triggered by PUS7 silencing. Furthermore, HSP90 was identified as a client protein of PUS7, associated with the increased PUS7 abundance in CRC. NMS-E973, a specific HSP90 inhibitor, also showed higher anti-metastatic activity when combined with PUS7 repression. Importantly, in line with these results, in human CRC tissues, the expression of PUS7 was positively linked to the expression of HSP90 and LASP1, and patients co-expressing HSP90/PUS7/LASP1 showed a worse prognosis. Conclusions The HSP90-dependent PUS7 upregulation promotes CRC cell metastasis via the regulation of LASP1. Thus, targeting the HSP90/PUS7/LASP1 axis may be a novel approach for the treatment of CRC.

scholarly journals Vitamin E beyond Its Antioxidant Label

Antioxidants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 634
Author(s):  
Anca Ungurianu ◽  
Anca Zanfirescu ◽  
Georgiana Nițulescu ◽  
Denisa Margină
Keyword(s):  
Vitamin E ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Protective Effects ◽  
Cellular Effects ◽  
Inflammatory Status ◽  
Anti Cancer ◽  
Key Factor ◽  
Exciting Potential ◽  
Underlying Mechanisms

Vitamin E, comprising tocopherols and tocotrienols, is mainly known as an antioxidant. The aim of this review is to summarize the molecular mechanisms and signaling pathways linked to inflammation and malignancy modulated by its vitamers. Preclinical reports highlighted a myriad of cellular effects like modulating the synthesis of pro-inflammatory molecules and oxidative stress response, inhibiting the NF-κB pathway, regulating cell cycle, and apoptosis. Furthermore, animal-based models have shown that these molecules affect the activity of various enzymes and signaling pathways, such as MAPK, PI3K/Akt/mTOR, JAK/STAT, and NF-κB, acting as the underlying mechanisms of their reported anti-inflammatory, neuroprotective, and anti-cancer effects. In clinical settings, not all of these were proven, with reports varying considerably. Nonetheless, vitamin E was shown to improve redox and inflammatory status in healthy, diabetic, and metabolic syndrome subjects. The anti-cancer effects were inconsistent, with both pro- and anti-malignant being reported. Regarding its neuroprotective properties, several studies have shown protective effects suggesting vitamin E as a potential prevention and therapeutic (as adjuvant) tool. However, source and dosage greatly influence the observed effects, with bioavailability seemingly a key factor in obtaining the preferred outcome. We conclude that this group of molecules presents exciting potential for the prevention and treatment of diseases with an inflammatory, redox, or malignant component.

scholarly journals Crocetin Mitigates Irradiation Injury in an In Vitro Model of the Pubertal Testis: Focus on Biological Effects and Molecular Mechanisms

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1676
Author(s):  
Giulia Rossi ◽  
Martina Placidi ◽  
Chiara Castellini ◽  
Francesco Rea ◽  
Settimio D'Andrea ◽  
...  
Keyword(s):  
In Vitro Model ◽  
Molecular Mechanisms ◽  
Biological Effects ◽  
Cellular Damage ◽  
X Rays ◽  
Adolescent Cancer ◽  
Radiation Induced ◽  
Vitro Model ◽  
Underlying Mechanisms

Infertility is a potential side effect of radiotherapy and significantly affects the quality of life for adolescent cancer survivors. Very few studies have addressed in pubertal models the mechanistic events that could be targeted to provide protection from gonadotoxicity and data on potential radioprotective treatments in this peculiar period of life are elusive. In this study, we utilized an in vitro model of the mouse pubertal testis to investigate the efficacy of crocetin to counteract ionizing radiation (IR)-induced injury and potential underlying mechanisms. Present experiments provide evidence that exposure of testis fragments from pubertal mice to 2 Gy X-rays induced extensive structural and cellular damage associated with overexpression of PARP1, PCNA, SOD2 and HuR and decreased levels of SIRT1 and catalase. A twenty-four hr exposure to 50 μM crocetin pre- and post-IR significantly reduced testis injury and modulated the response to DNA damage and oxidative stress. Nevertheless, crocetin treatment did not counteract the radiation-induced changes in the expression of SIRT1, p62 and LC3II. These results increase the knowledge of mechanisms underlying radiation damage in pubertal testis and establish the use of crocetin as a fertoprotective agent against IR deleterious effects in pubertal period.

scholarly journals Cathepsin B Localizes in the Caveolae and Participates in the Proteolytic Cascade in Trabecular Meshwork Cells. Potential New Drug Target for the Treatment of Glaucoma

2020 ◽  
Vol 10 (1) ◽  
pp. 78
Author(s):  
April Nettesheim ◽  
Myoung Sup Shim ◽  
Angela Dixon ◽  
Urmimala Raychaudhuri ◽  
Haiyan Gong ◽  
...  
Keyword(s):  
Trabecular Meshwork ◽  
Cathepsin B ◽  
Molecular Mechanisms ◽  
Culture Media ◽  
Ecm Remodeling ◽  
Trabecular Meshwork Cells ◽  
Proteolytic Cascade

Extracellular matrix (ECM) deposition in the trabecular meshwork (TM) is one of the hallmarks of glaucoma, a group of human diseases and leading cause of permanent blindness. The molecular mechanisms underlying ECM deposition in the glaucomatous TM are not known, but it is presumed to be a consequence of excessive synthesis of ECM components, decreased proteolytic degradation, or both. Targeting ECM deposition might represent a therapeutic approach to restore outflow facility in glaucoma. Previous work conducted in our laboratory identified the lysosomal enzyme cathepsin B (CTSB) to be expressed on the cellular surface and to be secreted into the culture media in trabecular meshwork (TM) cells. Here, we further investigated the role of CTSB on ECM remodeling and outflow physiology in vitro and in CSTBko mice. Our results indicate that CTSB localizes in the caveolae and participates in the pericellular degradation of ECM in TM cells. We also report here a novel role of CTSB in regulating the expression of PAI-1 and TGFβ/Smad signaling in TM cells vitro and in vivo in CTSBko mice. We propose enhancing CTSB activity as a novel therapeutic target to attenuate fibrosis and ECM deposition in the glaucomatous outflow pathway.

Exploring the molecular mechanisms of OSU-03012 on vascular smooth muscle cell proliferation

2010 ◽  
Vol 344 (1-2) ◽  
pp. 81-89 ◽  
Author(s):  
Wei-Wen Kuo ◽  
Jing-Ru Weng ◽  
Chih-Yang Huang ◽  
Chang-Hai Tsai ◽  
Wei-Hung Liu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Vascular Smooth Muscle Cell ◽  
Molecular Mechanisms ◽  
Smooth Muscle Cell Proliferation

Abstract 126: Differential Effects of Respectively Blocking Two BET Bromodomains on Vascular Smooth Muscle Cell Phenotype Transformation

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Mengxue Zhang ◽  
Bowen Wang ◽  
Craig Kent ◽  
Lian-Wang Guo
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Vascular Smooth Muscle Cell ◽  
Molecular Mechanisms ◽  
Cell Phenotype ◽  
Dependent Manner ◽  
Stat3 Phosphorylation ◽  
Phenotype Transformation

Introduction: Intimal hyperplasia (IH) occurs primarily due to vascular smooth muscle cell (SMC) transformation from quiescent to pathogenic phenotypes (e.g. proliferation and inflammation). Identification and effective targeting of key epigenetic factors governing SMC pathogenic transformation may lead to novel therapeutic methods for prevention of IH. We previously found that globally blocking the bromo- and extra-terminal (BET) epigenetic “reader” family abrogated SMC phenotype transformation and IH. We further investigated the functions of the two BET bromodomains (Bromo1 and Bromo2). Hypothesis: Bromo1 and Bromo2 play different roles in SMC pathogenic transformation. Methods and Results: We pre-treated rat primary aortic SMCs (for 2h) with Olinone or RVX208, inhibitors specific for Bromo1 and Bromo2 respectively, and then stimulated SMC phenotype transformation. Whereas RVX208 abrogated PDGF-BB-stimulated SMC proliferation (BrdU assay) in a dose dependent manner, Olinone enhanced SMC proliferation at high concentrations (>20 μM). RVX208 at 50 μM reduced TNFα-induced SMC inflammation (MCP-1 ELISA) by 80%,but Olinone at the same concentration slightly increased MCP-1. Furthermore, whereas RVX208 abolished PDGF-BB or TNFα-induced STAT3 phosphorylation (Western blotting), Olinone slightly increased phospho-STAT3. Conclusions: Our results reveal that blocking two BET bromodomains respectively produces distinct effects on SMC phenotype transformation, suggesting their differential epigenetic functions. Further elucidation of the underlying molecular mechanisms should contribute to precise targeting of the BET family for optimal mitigation of IH.

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