scholarly journals Knockdown of Microrna-1260 Promotes Up-Regulation of Both Collagen Type 1 Alpha 1 and Monocyte Chemoattractant Protein-1 in Vascular Smooth Muscle Cells from Human Abdominal Aortic Tissues

2020 ◽  
Vol 7 (1) ◽  
pp. 1103-1103
Author(s):  
Crystal Yin Tung CHAN ◽  
Bernice Lai Yee CHEUK ◽  
Stephen Wing Keung CHENG
Keyword(s):  
Smooth Muscle ◽  
Matrix Metalloproteinase ◽  
Collagen Type ◽  
Monocyte Chemoattractant Protein 1 ◽  
Monocyte Chemoattractant ◽  
Monocyte Chemoattractant Protein ◽  
Abdominal Aortic ◽  
Collagen Type 1

Objectives: MicroRNA (miR)-1260 was identified to be down-regulated in vascular smooth muscle cells (VSMCs) from human abdominal aortic aneurysm (AAA) tissues in our previous microarray profiling assay. MiR-1260 was predicted to target and down-regulate collagen type 1 alpha 1 (COL1A1), which is closely related to AAA formation, from a bioinformatics analysis. However, the role of miR-1260 in VSMCs for AAA formation still remains uncertain. This study aims to investigate the role of miR-1260 in human VSMCs. Methods: Stable overexpression and knockdown of miR-1260 using lentivirus were performed in VSMCs cultured from human abdominal aortic tissues. Expression of COL1A1 protein was investigated, followed by investigating the expressions of several key components involved in AAA pathogenic features: monocyte chemoattractant protein-1 (MCP-1) for inflammation; matrix metalloproteinase (MMP)-2, MMP-9, tissue inhibitor of matrix metalloproteinase (TIMP)- 1 and TIMP-2 for elastin fragmentation. Apoptosis of VSMCs was also examined. Results: Both COL1A1 and MCP-1 were significantly down-regulated upon miR-1260 overexpression, whereas they were significantly up-regulated upon miR-1260 knockdown. Neither protein expressions of MMP-2, MMP-9, TIMP-1 and TIMP-2 nor apoptosis were significantly different between miR-1260 overexpression/knockdown and corresponding controls. Conclusions: Our findings suggested suppression of miR-1260, which was previously found associated with AAA VSMCs, may promote up-regulation of COL1A1 and MCP-1 in human VSMCs, possibly promoting compensatory collagen synthesis and inflammation for AAA formation.

scholarly journals Host-Derived Smooth Muscle Cells Accumulate in Cardiac Allografts: Role of Inflammation and Monocyte Chemoattractant Protein 1

PLoS ONE ◽  
2009 ◽  
Vol 4 (1) ◽  
pp. e4187 ◽  
Author(s):  
Piotr Religa ◽  
Monika K. Grudzinska ◽  
Krzysztof Bojakowski ◽  
Joanna Soin ◽  
Jerzy Nozynski ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Monocyte Chemoattractant Protein 1 ◽  
Monocyte Chemoattractant ◽  
Monocyte Chemoattractant Protein ◽  
Cardiac Allografts

scholarly journals The Human Immunodeficiency Virus Type 1 Tat Protein Up-Regulates the Promoter Activity of the Beta-Chemokine Monocyte Chemoattractant Protein 1 in the Human Astrocytoma Cell Line U-87 MG: Role of SP-1, AP-1, and NF-κB Consensus Sites

2000 ◽  
Vol 74 (4) ◽  
pp. 1632-1640 ◽  
Author(s):  
Siew Pheng Lim ◽  
Alfredo Garzino-Demo
Keyword(s):  
Human Immunodeficiency Virus ◽  
Promoter Activity ◽  
Tat Protein ◽  
Monocyte Chemoattractant Protein 1 ◽  
Monocyte Chemoattractant ◽  
Monocyte Chemoattractant Protein ◽  
Astrocytoma Cell ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT It has been shown that the human immunodeficiency virus type 1 (HIV-1) Tat protein can specifically enhance expression and release of monocyte chemoattractant protein 1 (MCP-1) from human astrocytes. In this study, we show evidence that Tat-induced MCP-1 expression is mediated at the transcriptional level. Transient transfection of an expression construct encoding the full-length Tat into the human glioblastoma-astrocytoma cell line U-87 MG enhances reporter gene activity from cotransfected deletion constructs of the MCP-1 promoter. HIV-1 Tat exerts its effect through a minimal construct containing 213 nucleotides upstream of the translational start site. Site-directed mutagenesis studies indicate that an SP1 site (located between nucleotides −123 and −115) is critical for both constitutive and Tat-enhanced expression of the human MCP-1 promoter, as mutation of this SP1 site significantly diminished reporter gene expression in both instances. Gel retardation experiments further demonstrate that Tat strongly enhances the binding of SP1 protein to its DNA element on the MCP-1 promoter. Moreover, we also observe an increase in the binding activities of transcriptional factors AP1 and NF-κB to the MCP-1 promoter following Tat treatment. Mutagenesis studies show that an upstream AP1 site and an adjacent NF-κB site (located at −128 to −122 and −150 to −137, respectively) play a role in Tat-mediated transactivation. In contrast, a further upstream AP1 site (−156 to −150) does not appear to be crucial for promoter activity. We postulate that a Tat-mediated increase in SP1 binding activities augments the binding of AP1 and NF-κB, leading to synergistic activation of the MCP-1 promoter.

Abstract P771: Monocyte-Chemoattractant Protein-1 Levels in Human Carotid Atherosclerosis Associate With Hallmarks of Plaque Vulnerability

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Marios K Georgakis ◽  
Sander W van der Laan ◽  
Yaw Asare ◽  
Joost M Mekke ◽  
Saskia Haitjema ◽  
...  
Keyword(s):  
Leukocyte Adhesion ◽  
Intraplaque Hemorrhage ◽  
Vascular Risk ◽  
Plaque Vulnerability ◽  
Vascular Events ◽  
Monocyte Chemoattractant Protein 1 ◽  
Plaque Instability ◽  
Monocyte Chemoattractant ◽  
Monocyte Chemoattractant Protein

Background: Monocyte chemoattractant protein-1 (MCP-1) is a chemokine recruiting monocytes to the atherosclerotic plaque. Experimental, genetic, and epidemiological data support a key role of MCP-1 in atherosclerosis. Yet, the translational potential of targeting MCP-1 signaling for lowering vascular risk is limited by the lack of data on plaque MCP-1 activity in human atherosclerosis. Methods: We measured MCP-1 levels in human plaque samples from 1,199 patients undergoing carotid endarterectomy from the Athero-Express Biobank. We explored associations of plaque MCP-1 levels with histopathological features of plaque vulnerability, clinical plaque instability (symptomatic vs. asymptomatic plaque), molecular markers of plaque inflammation and remodeling, and with incident vascular events up to three years after plaque removal. Results: MCP-1 plaque levels were associated with individual histopathological hallmarks of plaque vulnerability (large lipid core, low collagen, high macrophage burden, low smooth muscle cell burden, intraplaque hemorrhage), as well as with a cumulative vulnerability index (range 0-5, beta: 0.42, 95%CI: 0.30-0.53, p=5.4x10 -13 ) independently of age, sex, and conventional vascular risk factors. Furthermore, MCP-1 levels were higher among patients with symptomatic, as compared to asymptomatic plaques (p=0.0001) and were associated with the levels of pro-inflammatory cytokines involved in leukocyte adhesion, as well as with matrix metalloproteinase activity in the plaque. In the follow-up analyses, MCP-1 levels were associated with a higher risk of peri-procedural events (up to 30 days after surgery). Conclusions: Our findings highlight a role of MCP-1 in human plaque vulnerability, the leading mechanism underlying vascular events like stroke and myocardial infarction. As such, they suggest that interfering with MCP-1 signaling in patients with established atherosclerosis could lower vascular risk.

scholarly journals Monocyte Chemoattractant Protein-1 (MCP-1/CCL2) Drives Activation of Bone Remodelling and Skeletal Metastasis

2019 ◽  
Vol 17 (6) ◽  
pp. 538-547 ◽  
Author(s):  
Bridie S. Mulholland ◽  
Mark R. Forwood ◽  
Nigel A. Morrison
Keyword(s):  
Breast Cancer Cells ◽  
Bone Remodelling ◽  
Skeletal Metastasis ◽  
Osteoclast Formation ◽  
Intermittent Treatment ◽  
Monocyte Chemoattractant Protein 1 ◽  
Monocyte Chemoattractant ◽  
Monocyte Chemoattractant Protein ◽  
Prostate Cancers

Abstract Purpose of Review The purpose of this review is to explore the role of monocyte chemoattractant protein-1 (MCP-1 or CCL2) in the processes that underpin bone remodelling, particularly the action of osteoblasts and osteoclasts, and its role in the development and metastasis of cancers that target the bone. Recent Findings MCP-1 is a key mediator of osteoclastogenesis, being the highest induced gene during intermittent treatment with parathyroid hormone (iPTH), but also regulates catabolic effects of continuous PTH on bone including monocyte and macrophage recruitment, osteoclast formation and bone resorption. In concert with PTH-related protein (PTHrP), MCP-1 mediates the interaction between tumour-derived factors and host-derived chemokines to promote skeletal metastasis. In breast and prostate cancers, an osteolytic cascade is driven by tumour cell–derived PTHrP that upregulates MCP-1 in osteoblastic cells. This relationship between PTHrP and osteoblastic expression of MCP-1 may drive the colonisation of disseminated breast cancer cells in the bone. Summary There is mounting evidence to suggest a pivotal role of MCP-1 in many diseases and an important role in the establishment of comorbidities. Coupled with its role in bone remodelling and the regulation of bone turnover, there is the potential for pathological relationships between bone disorders and bone-related cancers driven by MCP-1. MCP-1’s role in bone remodelling and bone-related cancers highlights its potential as a novel anti-resorptive and anti-metastatic target.

scholarly journals Regulation of Monocyte Chemoattractant Protein-1 Through Angiotensin II Type 1 Receptor in Prostate Cancer

2012 ◽  
Vol 180 (3) ◽  
pp. 1008-1016 ◽  
Author(s):  
Suguru Shirotake ◽  
Akira Miyajima ◽  
Takeo Kosaka ◽  
Nobuyuki Tanaka ◽  
Eiji Kikuchi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Angiotensin Ii ◽  
Monocyte Chemoattractant Protein 1 ◽  
Monocyte Chemoattractant ◽  
Monocyte Chemoattractant Protein
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