scholarly journals Fractalkine Preferentially Mediates Arrest and Migration of CD16+ Monocytes

2003 ◽  
Vol 197 (12) ◽  
pp. 1701-1707 ◽  
Author(s):  
Petronela Ancuta ◽  
Ravi Rao ◽  
Ashlee Moses ◽  
Andrew Mehle ◽  
Sunil K. Shaw ◽  
...  
Keyword(s):  
Chemokine Receptors ◽  
Molecular Mechanisms ◽  
Tissue Injury ◽  
Monocyte Subset ◽  
Blood Monocytes ◽  
Monocyte Chemoattractant Protein 1 ◽  
Pathological Conditions ◽  
Normal Individuals ◽  
And Migration

CD16+ monocytes represent 5–10% of peripheral blood monocytes in normal individuals and are dramatically expanded in several pathological conditions including sepsis, human immunodeficiency virus 1 infection, and cancer. CD16+ monocytes produce high levels of proinflammatory cytokines and may represent dendritic cell precursors in vivo. The mechanisms that mediate the recruitment of CD16+ monocytes into tissues remain unknown. Here we investigate molecular mechanisms of CD16+ monocyte trafficking and show that migration of CD16+ and CD16− monocytes is mediated by distinct combinations of adhesion molecules and chemokine receptors. In contrast to CD16− monocytes, CD16+ monocytes expressed high CX3CR1 and CXCR4 but low CCR2 and CD62L levels and underwent efficient transendo-thelial migration in response to fractalkine (FKN; FKN/CX3CL1) and stromal-derived factor 1α (CXCL12) but not monocyte chemoattractant protein 1 (CCL2). CD16+ monocytes arrested on cell surface–expressed FKN under flow with higher frequency compared with CD16− monocytes. These results demonstrate that FKN preferentially mediates arrest and migration of CD16+ monocytes and suggest that recruitment of this proinflammatory monocyte subset to vessel walls via the CX3CR1-FKN pathway may contribute to vascular and tissue injury during pathological conditions.

scholarly journals Cyr61 promotes Schwann cell proliferation and migration via αvβ3 integrin

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Zhenghui Cheng ◽  
Yawen Zhang ◽  
Yinchao Tian ◽  
Yuhan Chen ◽  
Fei Ding ◽  
...  
Keyword(s):  
Nerve Injury ◽  
Peripheral Nerves ◽  
Molecular Mechanisms ◽  
Αvβ3 Integrin ◽  
Promoting Effect ◽  
Ccn Family ◽  
And Migration ◽  
Proliferation And Migration

Abstract Background Schwann cells (SCs) play a crucial role in the repair of peripheral nerves. This is due to their ability to proliferate, migrate, and provide trophic support to axon regrowth. During peripheral nerve injury, SCs de-differentiate and reprogram to gain the ability to repair nerves. Cysteine-rich 61 (Cyr61/CCN1) is a member of the CCN family of matrix cell proteins and have been reported to be abundant in the secretome of repair mediating SCs. In this study we investigate the function of Cyr61 in SCs. Results We observed Cyr61 was expressed both in vivo and in vitro. The promoting effect of Cyr61 on SC proliferation and migration was through autocrine and paracrine mechanisms. SCs expressed αvβ3 integrin and the effect of Cyr61 on SC proliferation and migration could be blocked via αvβ3 integrin. Cyr61 could influence c-Jun protein expression in cultured SCs. Conclusions In this study, we found that Cyr61 promotes SC proliferation and migration via αvβ3 integrin and regulates c-Jun expression. Our study contributes to the understanding of cellular and molecular mechanisms underlying SC’s function during nerve injury, and thus, may facilitate the regeneration of peripheral nerves after injury.

Knockdown CYP2S1 inhibits lung cancer cells proliferation and migration

2021 ◽  
pp. 1-9
Author(s):  
Huan Guo ◽  
Baozhen Zeng ◽  
Liqiong Wang ◽  
Chunlei Ge ◽  
Xianglin Zuo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Cell Growth ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Lung Cancer Cells ◽  
Invasion And Migration ◽  
And Migration

BACKGROUND: The incidence of lung cancer in Yunnan area ranks firstly in the world and underlying molecular mechanisms of lung cancer in Yunnan region are still unclear. We screened a novel potential oncogene CYP2S1 used mRNA microassay and bioinformation database. The function of CYP2S1 in lung cancer has not been reported. OBJECTIVE: To investigate the functions of CYP2S1 in lung cancer. METHODS: Immunohistochemistry and Real-time PCR were used to verify the expression of CYP2S1. Colony formation and Transwell assays were used to determine cell proliferation, invasion and migration. Xenograft assays were used to detected cell growth in vivo. RESULTS: CYP2S1 is significantly up-regulated in lung cancer tissues and cells. Knockdown CYP2S1 in lung cancer cells resulted in decrease cell proliferation, invasion and migration in vitro. Animal experiments showed downregulation of CYP2S1 inhibited lung cancer cell growth in vivo. GSEA analysis suggested that CYP2S1 played functions by regulating E2F targets and G2M checkpoint pathway which involved in cell cycle. Kaplan-Meier analysis indicated that patients with high CYP2S1 had markedly shorter event overall survival (OS) time. CONCLUSIONS: Our data demonstrate that CYP2S1 exerts tumor suppressor function in lung cancer. The high expression of CYP2S1 is an unfavorable prognostic marker for patient survival.

scholarly journals An in vivo model allowing continuous observation of human vascular formation in the same animal over time

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yohei Tsukada ◽  
Fumitaka Muramatsu ◽  
Yumiko Hayashi ◽  
Chiaki Inagaki ◽  
Hang Su ◽  
...  
Keyword(s):  
Blood Vessel ◽  
Blood Vessels ◽  
Human Blood ◽  
Molecular Mechanisms ◽  
Human Tumor ◽  
Continuous Observation ◽  
In Vivo Models ◽  
Cranial Window ◽  
Pathological Conditions

AbstractAngiogenesis contributes to numerous pathological conditions. Understanding the molecular mechanisms of angiogenesis will offer new therapeutic opportunities. Several experimental in vivo models that better represent the pathological conditions have been generated for this purpose in mice, but it is difficult to translate results from mouse to human blood vessels. To understand human vascular biology and translate findings into human research, we need human blood vessel models to replicate human vascular physiology. Here, we show that human tumor tissue transplantation into a cranial window enables engraftment of human blood vessels in mice. An in vivo imaging technique using two-photon microscopy allows continuous observation of human blood vessels until at least 49 days after tumor transplantation. These human blood vessels make connections with mouse blood vessels as shown by the finding that lectin injected into the mouse tail vein reaches the human blood vessels. Finally, this model revealed that formation and/or maintenance of human blood vessels depends on VEGFR2 signaling. This approach represents a useful tool to study molecular mechanisms of human blood vessel formation and to test effects of drugs that target human blood vessels in vivo to show proof of concept in a preclinical model.

scholarly journals Pharmacological Effects and Potential Clinical Usefulness of Polyphenols in Benign Prostatic Hyperplasia

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 450
Author(s):  
Kensuke Mitsunari ◽  
Yasuyoshi Miyata ◽  
Tomohiro Matsuo ◽  
Yuta Mukae ◽  
Asato Otsubo ◽  
...  
Keyword(s):  
Benign Prostatic Hyperplasia ◽  
Molecular Mechanisms ◽  
Prostatic Hyperplasia ◽  
Pathological Conditions ◽  
Urinary Tract Symptoms ◽  
Anti Inflammatory ◽  
Lower Urinary

Benign prostatic hyperplasia (BPH) is arguably the most common benign disease among men. This disease is often associated with lower urinary tract symptoms (LUTS) in men and significantly decreases the quality of life. Polyphenol consumption reportedly plays an important role in the prevention of many diseases, including BPH. In recent years, in addition to disease prevention, many studies have reported the efficacy and safety of polyphenol treatment against various pathological conditions in vivo and in vitro. Furthermore, numerous studies have also revealed the molecular mechanisms of the antioxidant and anti-inflammatory effects of polyphenols. We believe that an improved understanding of the detailed pharmacological roles of polyphenol-induced activities at a molecular level is important for the prevention and treatment of BPH. Polyphenols are composed of many members, and their biological roles differ. In this review, we first provide information regarding the pathological roles of oxidative stress and inflammation in BPH. Next, the antioxidant and anti-inflammatory effects of polyphenols, including those of flavonoids and non-flavonoids, are discussed. Finally, we talk about the results and limitations of previous clinical trials that have used polyphenols in BPH, with particular focus on their molecular mechanisms of action.

scholarly journals Positive feedback between lncRNA FLVCR1-AS1 and KLF10 may inhibit pancreatic cancer progression via the PTEN/AKT pathway

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Jiewei Lin ◽  
Shuyu Zhai ◽  
Siyi Zou ◽  
Zhiwei Xu ◽  
Jun Zhang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Cancer Progression ◽  
Positive Feedback ◽  
Molecular Mechanisms ◽  
Tumor Tissues ◽  
And Migration

Abstract Background FLVCR1-AS1 is a key regulator of cancer progression. However, the biological functions and underlying molecular mechanisms of pancreatic cancer (PC) remain unknown. Methods FLVCR1-AS1 expression levels in 77 PC tissues and matched non-tumor tissues were analyzed by qRT-PCR. Moreover, the role of FLVCR1-AS1 in PC cell proliferation, cell cycle, and migration was verified via functional in vitro and in vivo experiments. Further, the potential competitive endogenous RNA (ceRNA) network between FLVCR1-AS1 and KLF10, as well as FLVCR1-AS1 transcription levels, were investigated. Results FLVCR1-AS1 expression was low in both PC tissues and PC cell lines, and FLVCR1-AS1 downregulation was associated with a worse prognosis in patients with PC. Functional experiments demonstrated that FLVCR1-AS1 overexpression significantly suppressed PC cell proliferation, cell cycle, and migration both in vitro and in vivo. Mechanistic investigations revealed that FLVCR1-AS1 acts as a ceRNA to sequester miR-513c-5p or miR-514b-5p from the sponging KLF10 mRNA, thereby relieving their suppressive effects on KLF10 expression. Additionally, FLVCR1-AS1 was shown to be a direct transcriptional target of KLF10. Conclusions Our research suggests that FLVCR1-AS1 plays a tumor-suppressive role in PC by inhibiting proliferation, cell cycle, and migration through a positive feedback loop with KLF10, thereby providing a novel therapeutic strategy for PC treatment.

scholarly journals METTL3 promotes the initiation and metastasis of ovarian cancer by inhibiting CCNG2 expression via promoting the maturation of pri-microRNA-1246

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Xuehan Bi ◽  
Xiao Lv ◽  
Dajiang Liu ◽  
Hongtao Guo ◽  
Guang Yao ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Molecular Mechanisms ◽  
High Expression ◽  
Ovarian Cancer Cells ◽  
Inadequate Knowledge ◽  
And Migration ◽  
Cancer Tissues

AbstractOvarian cancer is a common gynecological malignant tumor with a high mortality rate and poor prognosis. There is inadequate knowledge of the molecular mechanisms underlying ovarian cancer. We examined the expression of methyltransferase-like 3 (METTL3) in tumor specimens using RT-qPCR, immunohistochemistry, and Western blot analysis, and tested the methylation of METTL3 by MSP. Levels of METTL3, miR-1246, pri-miR-1246 and CCNG2 were then analyzed and their effects on cell biological processes were also investigated, using in vivo assay to validate the in vitro findings. METTL3 showed hypomethylation and high expression in ovarian cancer tissues and cells. Hypomethylation of METTL3 was pronounced in ovarian cancer samples, which was negatively associated with patient survival. Decreased METTL3 inhibited the proliferation and migration of ovarian cancer cells and promoted apoptosis, while METTL3 overexpression exerted opposite effects. Mechanistically, METTL3 aggravated ovarian cancer by targeting miR-1246, while miR-1246 targeted and inhibited CCNG2 expression. High expression of METTL3 downregulated CCNG2, promoted the metabolism and growth of transplanted tumors in nude mice, and inhibited apoptosis. The current study highlights the promoting role of METTL3 in the development of ovarian cancer, and presents new targets for its treatment.

scholarly journals Monocyte subset redistribution from blood to kidneys in patients with Puumala virus caused hemorrhagic fever with renal syndrome

2021 ◽  
Vol 17 (3) ◽  
pp. e1009400
Author(s):  
Sindhu Vangeti ◽  
Tomas Strandin ◽  
Sang Liu ◽  
Johanna Tauriainen ◽  
Anne Räisänen-Sokolowski ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Chemokine Receptors ◽  
Severe Disease ◽  
Hemorrhagic Fever ◽  
Puumala Virus ◽  
Monocyte Subset ◽  
Blood Monocytes ◽  
Peripheral Tissues ◽  
Hla Dr

Innate immune cells like monocytes patrol the vasculature and mucosal surfaces, recognize pathogens, rapidly redistribute to affected tissues and cause inflammation by secretion of cytokines. We previously showed that monocytes are reduced in blood but accumulate in the airways of patients with Puumala virus (PUUV) caused hemorrhagic fever with renal syndrome (HFRS). However, the dynamics of monocyte infiltration to the kidneys during HFRS, and its impact on disease severity are currently unknown. Here, we examined longitudinal peripheral blood samples and renal biopsies from HFRS patients and performed in vitro experiments to investigate the fate of monocytes during HFRS. During the early stages of HFRS, circulating CD14–CD16+ nonclassical monocytes (NCMs) that patrol the vasculature were reduced in most patients. Instead, CD14+CD16– classical (CMs) and CD14+CD16+ intermediate monocytes (IMs) were increased in blood, in particular in HFRS patients with more severe disease. Blood monocytes from patients with acute HFRS expressed higher levels of HLA-DR, the endothelial adhesion marker CD62L and the chemokine receptors CCR7 and CCR2, as compared to convalescence, suggesting monocyte activation and migration to peripheral tissues during acute HFRS. Supporting this hypothesis, increased numbers of HLA-DR+, CD14+, CD16+ and CD68+ cells were observed in the renal tissues of acute HFRS patients compared to controls. In vitro, blood CD16+ monocytes upregulated CD62L after direct exposure to PUUV whereas CD16– monocytes upregulated CCR7 after contact with PUUV-infected endothelial cells, suggesting differential mechanisms of activation and response between monocyte subsets. Together, our findings suggest that NCMs are reduced in blood, potentially via CD62L-mediated attachment to endothelial cells and monocytes are recruited to the kidneys during HFRS. Monocyte mobilization, activation and functional impairment together may influence the severity of disease in acute PUUV-HFRS.

scholarly journals Long Noncoding RNA HAGLROS Promotes Cell Invasion and Metastasis by Sponging miR-152 and Upregulating ROCK1 Expression in Osteosarcoma

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Kaifeng Zhou ◽  
Jun Xu ◽  
Xiaofan Yin ◽  
Jiangni Xia
Keyword(s):  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Luciferase Reporter ◽  
Tissue Samples ◽  
Normal Tissues ◽  
Tumor Growth And Metastasis ◽  
And Migration ◽  
Proliferation And Invasion

Background. Long noncoding RNAs (lncRNAs) played a crucial role in a number of biological processes. lncRNA HAGLROS was demonstrated to facilitate cell proliferation and migration in various cancers. However, the functions and molecular mechanisms of HAGLROS in osteosarcoma remained to be elucidated. Methods. qRT-PCR assay was used to detect the relative expression of HAGLROS in osteosarcoma tissue samples and cells. CCK-8 and Transwell assays were performed to assess the effects of HAGLROS on OS cells proliferation and invasion. Luciferase reporter assay verified the interaction between ROCK1 and miR-152. Results. In our study, we found that the expression of HAGLROS increased osteosarcoma samples and cell lines compared with normal tissues and cells. HAGLROS knockdown inhibited certain functions of U2OS and SW1353 cells in vitro. Moreover, HAGLROS depletion inhibited tumor growth and metastasis in vivo. Mechanically, we found that HAGLROS sponged miR-152 to promote ROCK1 expression in U2OS and SW1353 cells. Conclusion. In summary, our study indicated that HAGLROS could promote osteosarcoma progression by sponging miR-152 to promote ROCK1 expression. The results showed HAGLROS/miR-152/ROCK1 axis might act as a novel therapeutic strategy for osteosarcoma.

Pleiotropic roles of melatonin against oxidative stress mediated tissue injury in the gastrointestinal tract: An overview

2019 ◽  
Vol 2 (2) ◽  
pp. 158-184 ◽  
Author(s):  
Palash K Pal ◽  
Bharati Bhattacharjee ◽  
Aindrila Chattopadhyay ◽  
Debasish Bandyopadhyay
Keyword(s):  
Oxidative Stress ◽  
Molecular Mechanisms ◽  
Clinical Symptoms ◽  
Tissue Injury ◽  
Ischemia Reperfusion ◽  
Antioxidant Properties ◽  
Free Radical Scavenger ◽  
Radical Scavenger ◽  
Gi Tract ◽  
Pathological Conditions

The excessive production of free radicals and/or reactive oxygen species (ROS) in gastrointestinal (GI) tract leads to oxidative damages in GI tissues with development of varied pathological conditions and clinical symptoms. Many endogenous as well as exogenous factors are involved in such pathogenesis, herein, focus was given to the factors of metal toxicity, non-steroidal anti-inflammatory drugs (NSAIDs), ischemia-reperfusion, consumption of high fat diet and alcohol, and different pathological conditions and diseases. Since ROS is more or less involved in the GI damages caused by these factors, therefore attempts have been made to develop appropriate therapeutic agents that possess antioxidant properties. Being a potent antioxidant and free radical scavenger, melatonin was suggested as a potent therapeutic answer to these GI damages. The discovery of different binding sites and receptors of melatonin in the GI tissues further proves its local actions to protect these tissues from oxidative stress.  In the review, we attempt to try our best to summarize the current developments regarding the GI injuries caused by oxidative stress and the potential beneficial effects of melatonin on these injuries. The important molecular mechanisms associated with these changes were also highlighted in the discussion. We hope that this review will provide valuable information to consider melatonin as a suitable molecule used for GI tract protection.

Cellular and molecular mechanisms of HGF/Met in the cardiovascular system

2015 ◽  
Vol 129 (12) ◽  
pp. 1173-1193 ◽  
Author(s):  
Simona Gallo ◽  
Valentina Sala ◽  
Stefano Gatti ◽  
Tiziana Crepaldi
Keyword(s):  
Growth Factor ◽  
Blood Vessels ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Tissue Injury ◽  
Mitogen Activated Protein Kinase ◽  
Tyrosine Kinase Receptor ◽  
Ischaemic Injury ◽  
Protective Function

Met tyrosine kinase receptor, also known as c-Met, is the HGF (hepatocyte growth factor) receptor. The HGF/Met pathway has a prominent role in cardiovascular remodelling after tissue injury. The present review provides a synopsis of the cellular and molecular mechanisms underlying the effects of HGF/Met in the heart and blood vessels. In vivo, HGF/Met function is particularly important for the protection of the heart in response to both acute and chronic insults, including ischaemic injury and doxorubicin-induced cardiotoxicity. Accordingly, conditional deletion of Met in cardiomyocytes results in impaired organ defence against oxidative stress. After ischaemic injury, activation of Met provides strong anti-apoptotic stimuli for cardiomyocytes through PI3K (phosphoinositide 3-kinase)/Akt and MAPK (mitogen-activated protein kinase) cascades. Recently, we found that HGF/Met is also important for autophagy regulation in cardiomyocytes via the mTOR (mammalian target of rapamycin) pathway. HGF/Met induces proliferation and migration of endothelial cells through Rac1 (Ras-related C3 botulinum toxin substrate 1) activation. In fibroblasts, HGF/Met antagonizes the actions of TGFβ1 (transforming growth factor β1) and AngII (angiotensin II), thus preventing fibrosis. Moreover, HGF/Met influences the inflammatory response of macrophages and the immune response of dendritic cells, indicating its protective function against atherosclerotic and autoimmune diseases. The HGF/Met axis also plays an important role in regulating self-renewal and myocardial regeneration through the enhancement of cardiac progenitor cells. HGF/Met has beneficial effects against myocardial infarction and endothelial dysfunction: the cellular and molecular mechanisms underlying repair function in the heart and blood vessels are common and include pro-angiogenic, anti-inflammatory and anti-fibrotic actions. Thus administration of HGF or HGF mimetics may represent a promising therapeutic agent for the treatment of both coronary and peripheral artery disease.

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