CX3CL1/CX3CR1 Axis Contributes to Angiotensin II-Induced Vascular Smooth Muscle Cell Proliferation and Inflammatory Cytokine Production

Li, Chengsheng; He, Jin; Zhong, Xiaoyi; Gan, Hua; Xia, Yunlong

doi:10.1007/s10753-018-0736-4

Cited by 21 publications

(15 citation statements)

References 31 publications

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“…All six genes have previously been reported in the context of radiation or DNA damage response and fall into three main biological roles: cell cycle arrest, hemoglobin metabolism, and inflammatory response (Table 1 ). The prior relevant literature on Cdkn1a [ 53 , 54 ], Gdf15 [ 55 , 56 ], Ckap2 [ 57 , 58 ], Alas2 [ 59 , 60 ], Aplnr [ 61 , 62 ] and Cx3cr1 [ 63 , 64 ] are listed in Table 1 . We validated the expression of the most significantly upregulated and downregulated mRNAs in our data using RT-qPCR (Additional file 1 : Figure S1).…”

Section: Resultsmentioning

confidence: 99%

Analysis of lncRNA-miRNA-mRNA expression pattern in heart tissue after total body radiation in a mouse model

et al. 2021

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Background Radiation therapy is integral to effective thoracic cancer treatments, but its application is limited by sensitivity of critical organs such as the heart. The impacts of acute radiation-induced damage and its chronic effects on normal heart cells are highly relevant in radiotherapy with increasing lifespans of patients. Biomarkers for normal tissue damage after radiation exposure, whether accidental or therapeutic, are being studied as indicators of both acute and delayed effects. Recent research has highlighted the potential importance of RNAs, including messenger RNAs (mRNAs), microRNAs (miRNAs), and long non-coding RNAs (lncRNAs) as biomarkers to assess radiation damage. Understanding changes in mRNA and non-coding RNA expression will elucidate biological pathway changes after radiation. Methods To identify significant expression changes in mRNAs, lncRNAs, and miRNAs, we performed whole transcriptome microarray analysis of mouse heart tissue at 48 h after whole-body irradiation with 1, 2, 4, 8, and 12 Gray (Gy). We also validated changes in specific lncRNAs through RT-qPCR. Ingenuity Pathway Analysis (IPA) was used to identify pathways associated with gene expression changes. Results We observed sustained increases in lncRNAs and mRNAs, across all doses of radiation. Alas2, Aplnr, and Cxc3r1 were the most significantly downregulated mRNAs across all doses. Among the significantly upregulated mRNAs were cell-cycle arrest biomarkers Gdf15, Cdkn1a, and Ckap2. Additionally, IPA identified significant changes in gene expression relevant to senescence, apoptosis, hemoglobin synthesis, inflammation, and metabolism. LncRNAs Abhd11os, Pvt1, Trp53cor1, and Dino showed increased expression with increasing doses of radiation. We did not observe any miRNAs with sustained up- or downregulation across all doses, but miR-149-3p, miR-6538, miR-8101, miR-7118-5p, miR-211-3p, and miR-3960 were significantly upregulated after 12 Gy. Conclusions Radiation-induced RNA expression changes may be predictive of normal tissue toxicities and may indicate targetable pathways for radiation countermeasure development and improved radiotherapy treatment plans.

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Section: Resultsmentioning

confidence: 99%

Analysis of lncRNA-miRNA-mRNA expression pattern in heart tissue after total body radiation in a mouse model

et al. 2021

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“…These inflammatory cells in the intima were directly correlated with the number of CXCR1 + cells, most of which were VSMCs [30]. In addition, angiotensin II (Ang II) dysregulation was determined in many cardiovascular diseases, and it could upregulate CX3CR1 expression in VSMCs via the NADPH oxidase/ROS/p38 MAPK pathway [31]. Interestingly, CX3CL1 + and CX3CR1 + cells are also present in AAAs, indicating their contributions to the recruitment of inflammatory cells [32].…”

Section: Discussionmentioning

confidence: 99%

The potential role of chemotaxis and the complement system in the formation and progression of thoracic aortic aneurysms inferred from the weighted gene coexpression network analysis

et al. 2021

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Background Thoracic aortic aneurysm (TAA) can be life-threatening due to the progressive weakening and dilatation of the aortic wall. Once the aortic wall has ruptured, no effective pharmaceutical therapies are available. However, studies on TAA at the gene expression level are limited. Our study aimed to identify the driver genes and critical pathways of TAA through gene coexpression networks. Methods We analyzed the genetic data of TAA patients from a public database by weighted gene coexpression network analysis (WGCNA). Modules with clinical significance were identified, and the differentially expressed genes (DEGs) were intersected with the genes in these modules. Gene Ontology and pathway enrichment analyses were performed. Finally, hub genes that might be driving factors of TAA were identified. Furthermore, we evaluated the diagnostic accuracy of these genes and analyzed the composition of immune cells using the CIBERSORT algorithm. Results We identified 256 DEGs and two modules with clinical significance. The immune response, including leukocyte adhesion, mononuclear cell proliferation and T cell activation, was identified by functional enrichment analysis. CX3CR1, C3, and C3AR1 were the top 3 hub genes in the module correlated with TAA, and the areas under the curve (AUCs) by receiver operating characteristic (ROC) analysis of all the hub genes exceeded 0.7. Finally, we found that the proportions of infiltrating immune cells in TAA and normal tissues were different, especially in terms of macrophages and natural killer (NK) cells. Conclusion Chemotaxis and the complement system were identified as crucial pathways in TAA, and macrophages with interactive immune cells may regulate this pathological process.

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“…Ang II is widely used to induce hypertension and vascular remodeling as an animal model of hypertension [24–26]. It is well known that Ang II induces VSMC proliferation [27], which is widely used as a model of VSMC proliferation in vitro [28–30]. We found that BCL6 overexpression attenuated while BCL6 knockdown enhanced the Ang II-induced VSMC proliferation, indicating that BCL6 is an important protective factor in inhibiting Ang II-induced VSMC proliferation.…”

Section: Discussionmentioning

confidence: 99%

BCL6 Attenuates Proliferation and Oxidative Stress of Vascular Smooth Muscle Cells in Hypertension

Chen

Zang

Qiu

et al. 2019

Oxidative Medicine and Cellular Longevity

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Proliferation and oxidative stress of vascular smooth muscle cells (VSMCs) contribute to vascular remodeling in hypertension and several major vascular diseases. B-cell lymphoma 6 (BCL6) functions as a transcriptional repressor. The present study is designed to determine the roles of BCL6 in VSMC proliferation and oxidative stress and underlying mechanism. Angiotensin (Ang) II was used to induce VSMC proliferation and oxidative stress in human VSMCs. Effects of BCL6 overexpression and knockdown were, respectively, investigated in Ang II-treated human VSMCs. Therapeutical effects of BCL6 overexpression on vascular remodeling, oxidative stress, and proliferation were determined in the aorta of spontaneously hypertensive rats (SHR). Ang II reduced BCL6 expression in human VSMCs. BCL6 overexpression attenuated while BCL6 knockdown enhanced the Ang II-induced upregulation of NADPH oxidase 4 (NOX4), production of reactive oxygen species (ROS), and proliferation of VSMCs. BCL6 expression was downregulated in SHR. BCL6 overexpression in SHR reduced NOX4 expression, ROS production, and proliferation of the aortic media of SHR. Moreover, BCL6 overexpression attenuated vascular remodeling and hypertension in SHR. However, BCL6 overexpression had no significant effects on NOX2 expression in human VSMCs or in SHR. We conclude that BCL6 attenuates proliferation and oxidative stress of VSMCs in hypertension.

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CX3CL1/CX3CR1 Axis Contributes to Angiotensin II-Induced Vascular Smooth Muscle Cell Proliferation and Inflammatory Cytokine Production

Cited by 21 publications

References 31 publications

Analysis of lncRNA-miRNA-mRNA expression pattern in heart tissue after total body radiation in a mouse model

Analysis of lncRNA-miRNA-mRNA expression pattern in heart tissue after total body radiation in a mouse model

The potential role of chemotaxis and the complement system in the formation and progression of thoracic aortic aneurysms inferred from the weighted gene coexpression network analysis

BCL6 Attenuates Proliferation and Oxidative Stress of Vascular Smooth Muscle Cells in Hypertension

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