BIOMEDICINE & PHARMACOTHERAPY
·
2024
·
IF 6.9
Jian Zhang,Xinlin Li,Wenqing Cui,Dingchun Lu,Yanyan Zhang,Jiajia Liao,Linlin Guo,Chunen Jiao,Ling Tao,Yini Xu,Xiangchun Shen
Accumulating evidence strongly support the key role of NLRP3-mediated pyroptosis in the pathogenesis and progression of vascular endothelial dysfunction associated with diabetes mellitus. Various studies have demonstrated that the activation or upregulation of Silent Information Regulation 2 homolog 2 (SIRT2) exerts inhibitory effect on the expression of NLRP3. Although 1,8-cineole has been found to protect against endothelial dysfunction and cardiovascular diseases, its role and mechanism in diabetic angiopathy remain unknown. Therefore, the aim of this study was to investigate the ameliorative effect of 1,8-cineole through SIRT2 on pyroptosis associated with diabetic angiopathy in human umbilical vein endothelial cells (HUVECs) and to elucidate the underlying mechanism. The findings revealed that 1,8-cineole exhibited a protective effect against vascular injury and ameliorated pathological alterations in the thoracic aorta of diabetic mice. Moreover, it effectively mitigated pyroptosis induced by palmitic acid-high glucose (PA-HG) in HUVECs. Treatment with 1,8-cineole effectively restored the reduced levels of SIRT2 and suppressed the elevated expression of pyroptosis-associated proteins. Additionally, our findings demonstrated the occurrence of NLRP3 deacetylation and the physical interaction between NLRP3 and SIRT2. The SIRT2 inhibitor AGK2 and siRNA-SIRT2 effectively attenuated the effect of 1,8-cineole on NLRP3 deacetylation in HUVECs and compromised its inhibitory effect against pyroptosis in HUVECs. However, overexpression of SIRT2 inhibited PA-HG-induced pyroptosis in HUVECs. 1,8-Cineole inhibited the deacetylation of NLRP3 by regulating SIRT2, thereby reducing pyroptosis in HUVECs. In conclusion, our findings suggest that PA-HG-induced pyroptosis in HUVECs plays a crucial role in the development of diabetic angiopathy, which can be mitigated by 1,8-cineole.
研究领域:
药理学
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糖尿病
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血管生物学
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炎症
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Stem Cell Research & Therapy
·
2020
·Vol. 11
·期 1
·1-13
·
IF 5.116
Chai Miaomiao,Gu Ce,Shen Qihua,Liu Jiaxing,Zhou Yi,Jin Ziyang,Xiong Wanli,Zhou Yan,Tan Wensong
Background and aim Inadequate vascularization is a challenge in bone tissue engineering because internal cells are prone to necrosis due to a lack of nutrient supply. Rat bone marrow-derived mesenchymal stem cells (rBMSCs) and human umbilical vein endothelial cells (HUVECs) were cocultured to construct prevascularized bone tissue in osteogenic induction medium (OIM) in vitro. The angiogenic capacity of HUVECs was limited in the coculture system. In this study, the effects of the components in the medium on HUVEC angiogenesis were analyzed. Methods The coculture system was established in OIM. Alizarin red staining and alkaline phosphatase staining were used to assess the osteogenic ability of MSCs. A Matrigel tube assay was used to assess the angiogenic ability of HUVECs in vitro. The proliferation of HUVECs was evaluated by cell counting and CCK-8 assays, and migration was evaluated by the streaked plate assay. The expression levels of angiogenesis-associated genes and proteins in HUVECs were measured by qRT-PCR and Western blotting, respectively. Results Dexamethasone in the OIM suppressed the proliferation and migration of HUVECs, inhibiting the formation of capillary-like structures. Our research showed that dexamethasone stimulated HUVECs to secrete tissue inhibitor of metalloproteinase (TIMP-3), which competed with vascular endothelial growth factor (VEGF-A) to bind to vascular endothelial growth factor receptor 2 (VEGFR2, KDR). This effect was related to inhibiting the phosphorylation of ERK and AKT, which are two downstream targets of KDR. However, under hypoxia, the enhanced expression of hypoxia-inducible factor-1α (HIF-1α) decreased the expression of TIMP-3 and promoted the phosphorylation of KDR, improving HUVEC angiogenesis in the coculture system. Conclusion Coculture of hypoxia-preconditioned HUVECs and MSCs showed robust angiogenesis and osteogenesis in OIM, which has important implications for prevascularization in bone tissue engineering in the future.
研究领域:
组织工程
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细胞生物学
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分子生物学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
MICROVASCULAR RESEARCH
·
2021
·
IF 3.514
Yi-hua Zhou,Yu-zhi Tang,Liang-yun Guo,Li-li Zheng,Dan Zhang,Can-ying Yang,Wei Wang
Soluble fms-like tyrosine kinase-1 (sFlt-1), a circulating antiangiogenic protein, is involved in the pathogenesis of atherosclerosis (AS), and the underlying mechanism is still unclear. Here, we attempted to investigate the mechanism of action of sFlt-1 in AS. Human umbilical vein endothelial cells (HUVECs) were treated with oxidized low density lipoprotein (ox-LDL) to induce cell injury. ox-LDL treatment increased LC3-II/LC3-I ratio, Beclin-1 expression and GFP-LC3 puncta in HUVECs, suggesting that ox-LDL may induce autophagic flux impairment in HUVECs. ox-LDL-treated HUVECs displayed a decrease of sFlt-1 levels. Moreover, ox-LDL treatment reduced cell proliferation and elevated apoptosis in HUVECs, which was abrogated by sFlt-1 overexpression. Up-regulation of sFlt-1 repressed the activity of PI3K/AKT/mTOR signaling pathway and enhanced autophagy in HUVECs following ox-LDL treatment. Additionally, sFlt-1 overexpression-mediated increase of autophagy in ox-LDL-treated HUVECs was abolished by 3-methyladenine (autophagy inhibitor). 3-methyladenine abrogated the impact of sFlt-1 overexpression on proliferation and apoptosis in ox-LDL-treated HUVECs. This work confirmed that overexpression of sFlt-1 activated autophagy by repressing PI3K/Akt/mTOR signaling pathway, and thus alleviated ox-LDL-induced injury of HUVECs. Therefore, this study suggests that sFlt-1 may be a potential target for AS treatment.
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产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2023
·Vol. 13
·期 17
·11269-11277
·
IF 3.9
Shengnan Ma,Lei Song,Yueyue Bai,Shihao Wang,Jiao Wang,Haohao Zhang,Fazhan Wang,Yiyan He,Chuntao Tian,Guijun Qin
Exosomes exhibit great potential as novel therapeutics for tissue regeneration, including cell migration and angiogenesis. However, the limited intracellular delivery efficiency of exosomes might reduce their biological effects. Here, exosomes secreted by adipose-derived mesenchymal stem cells were recombined with fluorinated peptide dendrimers (FPG3) to form the fluorine-engineered exosomes (exo@FPG3), which was intended to promote the cytosolic release and the biological function of exosomes. The mass ratio of FPG3 to exosomes at 5 was used to investigate its cellular uptake efficiency and bioactivity in HUVECs, as the charge of exo@FPG3 tended to be stable even more FPG3 was applied. It was found that exo@FPG3 could enter HUVECs through a variety of pathways, in which the clathrin-mediated endocytosis played an important role. Compared with exosomes modified with peptide dendrimers (exo@PG3) and exosomes alone, the cellular uptake efficiency of exo@FPG3 was significantly increased. Moreover, exo@FPG3 significantly enhanced the angiogenesis and migration of HUVECs in vitro as compared to exo@PG3 and exosomes. It is concluded that surface fluorine modification of exosomes with FPG3 is conducive to the cellular uptake and bioactivity of the exosome, which provides a novel strategy for engineered exosomes to enhance the biological effects of exosome-based drug delivery.
研究领域:
组织工程
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药物递送
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细胞生物学
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干细胞研究
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2019
·
IF 3.571
Fang Gong,Mei-Fang Chen,Jiali Chen,ChengYong Li,ChunXia Zhou,PengZhi Hong,ShengLi Sun,Zhong-Ji Qian
Abalone (Haliotis discus hannai) is a precious seafood in the market. It has been reported that biological active substances derived from abalone have anti-oxidative, anti-inflammatory, anti-bacterial, and anti-thrombosis potential. However, there were few studies to assess whether they have anti-cancer potential. In this study, we evaluated the anti-metastasis and anti-pro-angiogenic factors and mechanism of action of boiled abalone byproduct peptide (BABP, EMDEAQDPSEW) in human fibrosarcoma (HT1080) cells and human umbilical vein endothelial cells (HUVECs). The results demonstrated that BABP treatment significantly lowers migration and the invasion of HT1080 cells and HUVECs. BABP inhibits phorbol 12-myristate 13-acetate (PMA)-induced matrix metalloproteinase (MMP) expression and activity by blocking mitogen-activated protein kinases (MAPKs) and NF-κB signaling and hypoxia-induced vascular endothelial growth factor (VEGF) secretion and hypoxia inducible factor (HIF)-1α accumulation through suppressing the AKT/mTOR signal pathway. BABP treatment inhibits VEGF-induced VEGFR-2 expression and tube formation in HUVECs. The effect of BABP on anti-metastatic and anti-vascular activity in HT1080 cells and HUVECs revealed that BABP may be a potential pharmacophore for tumor therapy in the future.
研究领域:
肿瘤学
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药理学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
CELL AND TISSUE RESEARCH
·
2023
·
IF 3.6
Yuan Haojie,Yu Junbo,Liu Chun,Zhao Heyan,Xue Jianhua,Liu Jiajia,Yang Yang
This study aims to discuss the role of exosomes KCNQ10T1 derived from bone marrow mesenchymal stem cells (BMMSCs) in sepsis and to further investigate its potential molecular mechanisms. Exosomes extracted from BMMSCs are identified by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and western blot. Fluorescence labeling is applied to detect the internalization of exosomes in receptors. The proliferation ability, migration ability, and invasion ability of HUVECs are determined by CCK-8, EdU, wound healing, and Transwell. The levels of inflammatory cytokines in sepsis cells are quantitatively detected by ELISA. Kaplan–Meier survival curve is used to describe the overall survival. RT-qPCR is used to detect mRNA expression of related genes. Bioinformatics analysis is performed to search the downstream target of KCNQ1OT1 and miR-154-3p and the interaction is verified by luciferase reporter assay. Exosomes derived from BMMSCs alleviated the toxicity in sepsis cell models and animal models. In mice with septic cell models, exosomal KCNQ10T1 was down-regulated and associated with lower survival. Overexpression of KCNQ10T1 inhibited the proliferation and metastasis of LPS-induced HUVECs. Further research illustrated that miR-154-3p was the downstream target gene of KCNQ1OT1 and RNF19A was the downstream target gene of miR-154-3p. Importantly, functional research findings indicated that KCNQ1OT1 regulated sepsis progression by targeting miR-154-3p/RNF19A axis. Our study demonstrates that the exosomal KCNQ1OT1 suppresses sepsis via mediating miR-154-3p/RNF19A, which provides a latent target for sepsis treatment.
研究领域:
分子生物学
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干细胞研究
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免疫学
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细胞生物学
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医学遗传学
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DOI
PubMed
高影响因子
Biomaterials Science
·
2021
·Vol. 9
·期 16
·5519-5532
·
IF 6.843
Qiyuan Dai,Qingtao Li,Huichang Gao,Longtao Yao,Zefeng Lin,Dingguo Li,Shuangli Zhu,Cong Liu,Zhen Yang,Gang Wang,Dafu Chen,Xiaofeng Chen,Xiaodong Cao
The increasing insight into the molecular and cellular processes within the angiogenic cascade assists in enhancing the survival and integration of engineered bone constructs. Copper-doped bioactive glass (Cu-BG) is now a potential structural component of the novel scaffolds and implants used in orthopedic and dental repairs. However, it is difficult for BG, especially micro-nano particles, to be printed into scaffolds and still retain its biological activity and ability to biodegrade. Additionally, the mechanisms of the copper-stimulating autocrine and paracrine effects of human umbilical vein endothelial cells (hUVECs) during repair and regeneration of bone are not yet clear. Therefore, in this study, we created monodispersed micro-nano spherical Cu-BG particles with varying copper content through a sol–gel process. Through in vitro tests, we found that Cu-BG enhanced angiogenesis by activating the pro-inflammatory environment and the HIF-1α pathway of hUVECs. Furthermore, 2Cu-BG diluted extracts directly promoted the osteogenic differentiation of mouse bone mesenchymal stem cells (BMSCs) in vitro. Then, a new 3D-printed tyramine-modified gelatin/silk fibroin/copper-doped bioactive glass (Gel/SF/Cu-BG) scaffold for rat bone defects was constructed, and the mechanism of the profound angiogenesis effect regulated by copper was explored in vivo. Finally, we found that hydrogel containing 1 wt% 2Cu-BG effectively regulated the spatiotemporal coupling of vascularization and osteogenesis. Therefore, Cu-BG-containing scaffolds have great potential for a wide range of bone defect repairs.
研究领域:
生物医学工程
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组织工程
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骨科
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材料科学
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2024
·
IF 4.4
Lan Tian,Duan Guozhen,Qi Youchao,Almezgagi Maged,Fan Guanghui,Ma Yonggui
Wolfberry, esteemed as a traditional Chinese medicinal material and functional food, is replete with nutrients and boasts a diverse array of health benefits, including hypoglycemic, antitumor, antioxidant, anti-inflammatory, and immune-enhancing properties. Notably, inflammation is a pivotal factor in the onset and progression of numerous diseases. Despite this, there is a paucity of research on the comprehensive evaluation of the components found in different wolfberries, and the exploration of their primary active components is limited. To address this issue, we conducted a comprehensive targeted metabolomics analysis, employing statistical methods such as principal component analysis (PCA), orthogonal partial least squares discriminant analysis (OPLS-DA), KEGG pathway analysis, and volcano plots to delineate the compositional differences among red, black, and yellow wolfberries. Furthermore, we investigated the anti-inflammatory effects of their primary components through in vitro experiments. Our analysis revealed a total of 1,104 chemical compositions in the three wolfberries, with alkaloids, phenolic acids, flavonoids, and lipids being the predominant nutritional components. KEGG enrichment analysis indicated that these compositions were primarily involved in the biosynthesis of secondary metabolites, ABC transport, and galactose metabolism pathway. Moreover, our study demonstrated that quercetin exhibited dose-dependent anti-inflammatory activity in LPS-stimulated HUVECs. It effectively inhibited the production of inflammatory factors such as TNF-α, MCP-1, and IL-1β, while also down-regulating the gene and protein expression levels of ICAM-1 and VCAM-1. In conclusion, our findings indicate that there are variations in compositions among the three wolfberries, with flavonoids being the most abundant, and in vitro studies also confirmed the anti-inflammatory potential of quercetin. It is worth noting that Lycium ruthenicum contains higher levels of antioxidant components and possesses greater nutritional value, providing valuable insights for the future development and utilization of the three wolfberries.
研究领域:
药理学
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代谢组学
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生物化学
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药物化学
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植物科学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACOLOGICAL SCIENCES
·
2015
·
IF 2.36
Fang Li,Yi-Sha Tan,Hong-Lin Chen,Yan Yan,Ke-Feng Zhai,Da-Peng Li,Jun-Ping Kou,Bo-Yang Yu
YiQiFuMai Powder Injection (YQFM) is a re-developed preparation based on the well-known traditional Chinese medicine formula Sheng-mai-san. It has been widely used for the treatment of cardiovascular disease with definite clinical efficacy in China, but its bioactive molecules remain obscure. In this study, an effective method has been employed as a tool for screening active components in YQFM, using human umbilical vein endothelial cells (HUVECs) extraction and liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (Q-TOF MS/MS). Nine compounds, which could interact with HUVECs, were identified as ginsenosides Rb1, Rc, Rb2, Rd, 20(S)-Rg3, 20(R)-Rg3, Rk1/Rg5 and schisandrin by comparing with reference substances or literature. In vitro assays showed that schisandrin at concentrations of 10–100 μM protected HUVECs from hypoxia/reoxygenation (H/R) injury, increased cell viability, nitric oxide (NO) content and decreased lactate dehydrogenase (LDH) leakage, malonaldehyde (MDA) content and ROS generation. Moreover, schisandrin pretreatment inhibited cell apoptosis, as evidenced by inhibiting activation of caspase-3 and increasing the Bcl-2/Bax ratio. These data indicate that HUVECs biospecific extraction coupled with HPLC-ESI-Q-TOF-MS/MS analysis is a reliable method for screening potential bioactive components from traditional Chinese medicines. Meanwhile, the vascular endothelium protective property of schisandrin might be beneficial for the treatment of cardiovascular disease.
研究领域:
药理学
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心血管科学
·
中药学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-19
·
IF 10.6
Luo Yuxiao,Zheng Yifan,Chen Ziwei,Mo Minhua,Xie Jiling,Zhou Xiaohe,Wu Yupeng,Yang Qiyuan,Zheng Manjia,Hu Xiaowen,Chen Liangjiao,Lan Zedong
Background Early angiogenesis provides nutrient supply for bone tissue repair, and insufficient angiogenesis will lead tissue engineering failure. Lanthanide metal nanoparticles (LM NPs) are the preferred materials for tissue engineering and can effectively promote angiogenesis. Holmium oxide nanoparticles (HNPs) are LM NPs with the function of bone tissue “tracking” labelling. Preliminary studies have shown that HNPs has potential of promote angiogenesis, but the specific role and mechanism remain unclear. This limits the biological application of HNPs. Results In this study, we confirmed that HNPs promoted early vessel formation, especially that of H-type vessels in vivo, thereby accelerating bone tissue repair. Moreover, HNPs promoted angiogenesis by increasing cell migration, which was mediated by filopodia extension in vitro. At the molecular level, HNPs interact with the membrane protein EphrinB2 in human umbilical vein endothelial cells (HUVECs), and phosphorylated EphrinB2 can bind and activate VAV2, which is an activator of the filopodia regulatory protein CDC42. When these three molecules were inhibited separately, angiogenesis was reduced. Conclusion Overall, our study confirmed that HNPs increased cell migration to promote angiogenesis for the first time, which is beneficial for bone repair. The EphrinB2/VAV2/CDC42 signalling pathway regulates cell migration, which is an important target of angiogenesis. Thus, HNPs are a new candidate biomaterial for tissue engineering, providing new insights into their biological application.
研究领域:
生物医学工程
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组织工程
·
纳米技术
·
细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
MACROMOLECULAR BIOSCIENCE
·
2013
·Vol. 13
·期 4
·483-493
·
IF 3.742
Jin-Lei Wang,Ke-Feng Ren,Hao Chang,Fan Jia,Bo-Chao Li,Ying Ji,Jian Ji
Mussel-inspired poly(dopamine) (PDA) coating is proven to be a simple, versatile, and effective strategy to promote cell adhesion onto various substrates. In this study, the initial adhesive behavior of human umbilical vein endothelial cells (HUVECs) is evaluated on a PDA coating under serum-free conditions. It is found that HUVECs can attach directly to and spread with well-organized cytoskeleton and fibrillar adhesions on the PDA surface, whereas cells adhere poorly to and barely spread on the control polycaprolactone surface. Endogenous fibronectin and α 5 β 1 integrin are found to be involved in the cell adhesion process. These findings will lead to a better understanding of interactions between cells and PDA coating, paving the way for the further development of PDA.
研究领域:
生物材料
·
细胞生物学
·
组织工程
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DOI
PubMed
高影响因子
LABORATORY INVESTIGATION
·
2018
·Vol. 98
·期 12
·1642-1656
·
IF 4.263
Cao Zhanqi,Hao Zhaojun,Xin Ming,Yu Lugang,Wang Lei,Zhang Ying,Zhang Xinke,Guo Xiuli
Tumor cell-endothelial adhesion is one of the key steps in tumor cell haematogenous dissemination in metastasis and was previously shown to be mediated by interaction of galectin-3 with the transmembrane mucin protein MUC1. In this study, the effect of exogenous as well as endogenous galectin-3 on adhesion of two cell lines (low MUC1-expressing human prostate cancer PC-3M cells and non-small-cell lung cancer A549 cells) to monolayer of umbilical vein endothelial cells (HUVECs) was investigated. We found that suppression of endogenous galectin-3 expression reduced tumor cell adhesion to HUVECs and also decreased cell invasion and migration. Exogenous galectin-3 promoted tumor cell adhesion to HUVECs by entering cells. Both exogenous and endogenous galectin-3 upregulated the expression of β-catenin and increased β-catenin nuclear accumulation, and subsequently upregulated the expression of N-cadherin and CD44. We deduced that both exogenous as well as endogenous galectin-3 promoted low MUC1-expressing cancer cell adhesion to HUVECs by increasing the expression of N-cadherin and CD44 via an increase of nuclear β-catenin accumulation. These results were confirmed further by using a β-catenin/TCF transcriptional activity inhibitor, N-cadherin or CD44 siRNAs. Taken together, our results suggest a new molecular mechanism of galectin-3-mediated cell adhesion in cancer metastasis.
研究领域:
肿瘤学
·
细胞生物学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）