scholarly journals MicroRNA-30a-5p-Mediated Autophagy Regulates Formation of Foam Cells from THP-1-derived Macrophages

Author(s):  
Chunhui Geng ◽  
Chao Wang ◽  
Guangming Su ◽  
Shengjiao Wang ◽  
Jiashan Li ◽  
...  

Abstract MicroRNAs are widely considered to be involved in the pathogenesis of atherosclerosis. Whereas the importance of miR-30a-5p as a tumor growth-promoting factor has been extensively studied, the relationship between this particular microRNA and atherosclerosis remains to be clarified. In this study, the role of miR-30a-5p in the formation of foam cells from THP-1-derived macrophages was investigated. It was found that miR-30a-5p could robustly regulate the pathological process of atherosclerosis by inhibiting autophagy and increasing the accumulation of lipids, the expression of inflammatory factors, and the apoptosis of macrophages. These results provide guidance for future assessments of the progression of atherosclerosis and for the development of intervention targets for the treatment of this disease.

2020 ◽  
Author(s):  
Aimei Liu ◽  
Feng Zhu ◽  
Xiaohui Zhu ◽  
Yulian Wang ◽  
Awais Ihsan ◽  
...  

Abstract Background: Cyadox is an effective growth-promoting antibiotic, which is similar to the role of recombinant growth hormone (rGH). Current studies have shown that cyadox can promote animal growth through altering intestinal microflora, improving protein utilization and increasing protein synthesis. Increasing evidence suggests that epigenetics are also closely related to growth. However, the potential role of epigenetics in the cyadox for growth has not been explored. Results: Here, we used recombinant growth hormone (rGH) and cyadox to study the relationship between growth and changes in epigenetics including DNA methylation, histone modification and chromatin structure. Bisulfite DNA sequencing (BSP) assay suggested that cyadox and rGH treatments increased IGF-1 expression partially by hypomethylation at CpG sites within the promoter region of IGF-1, which was regulated by DNA methyltransferases (DNMTs). We also observed an enrichment of H3K4me3 and H3K27ac at the promoter regions of IGF-1 by ChIP-qPCR assay, which contributed to an increase in IGF-1 transcription. In addition, immunofluorometric assay displayed cellular accessible chromatin structure following the treatment of cyadox and rGH, facilitating the combination of transcription factors and DNA and thus enhancing gene transcription. Conclusions: Taken together, our findings indicated that cyadox and rGH promote cell growth partially through epigenetic changes, providing a prospect for the development of animal growth-promoting drugs in the future.


2020 ◽  
Vol 28 ◽  
Author(s):  
Lei Chen ◽  
Ying-Jian Gu ◽  
Ming-Yuan Zhou ◽  
Lin Cheng ◽  
Yun Wang

Background: Pulmonary arterial hypertension is one of the chronic diseases that affect the human health. Microvesicles participate in the communication between cells by fusing with the recipient cells to transfer the bioactive molecules, such as lipids, proteins, RNA, etc., to the target cells. Microvesicles are involved in various biological processes, and have the functions of regulating immunity, promoting angiogenesis and so on. Microvesicles derived from various cells may become diagnostic biomarkers or therapeutic targets to the diseases. Therefore, exploring the role of microvesicles-mediated cell communication has become a potential therapeutic target to pulmonary arterial hypertension. Objective: It is to clarify the classification, features and mechanism of microvesicles in cell communication, and to discuss the potential important roles of microvesicles-mediated cell communication in pulmonary arterial hypertension. Results: Inflammation is an important the pathogenesis of pulmonary arterial hypertension. Many studies have shown that microvesicles from different cells can participate in the pathological process of PAH by transferring the inflammatory factors contained in them. Conclusion: Microvesicles-mediated cell communication may become the therapeutic target to pulmonary arterial hypertension.


2018 ◽  
Vol 2018 ◽  
pp. 1-9
Author(s):  
Xianlun Pang ◽  
Jiang Yang ◽  
Xiaoli Zhen ◽  
Hai Nie ◽  
Hao Qin ◽  
...  

UHMWPE granule could induce macrophages and inflammatory responses in interfacial tissues, which eliminated the wear debris of UHMWPE component and further induced dissolution of the surrounding bone, leading aseptic loosening. However, the mechanism of synovial cells, especially fibroblast-like synovial (FLS) cells response to UHMWPE, remains unknown. Herein we choose FLS cells as research object. Vimentin (+) CD68 (-) was identified by flow cytometry and immunofluorescent staining assay, and the cells were identified as FLS cells, which was consistent with the experimental requirements. The inhibitory evaluation showed that UHMWPE could significantly promote the proliferation and inhibit apoptosis of FLS cells in dose- and time-dependent manners and increase the levels of proinflammatory cytokines, including IL-6, IL-1β, TNF-α, PGE2, MMP2, and LOX. UHMWPE also can induce the expression of mIL-6R protein in FLS cells and further investigate the relationship between apoptosis and inflammation. Interestingly enough, when we added the interleukin-6 receptor antagonist (IL-6RA), the expression levels of proapoptosis-related proteins increased; in other words, UHMWPE-induced antiapoptosis diminished by IL-6RA (50 μg/ml). Taken together, these findings clearly demonstrated that UHMWPE promote growth in FLS cells through upregulating inflammatory factors to produce antiapoptotic effect.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Zulvikar Syambani Ulhaq ◽  
Gita Vita Soraya ◽  
Budu ◽  
Lely Retno Wulandari

Abstract Interleukin-6 (IL-6) is one of the key regulators behind the inflammatory and pathological process associated with ophthalmic diseases. The role of IL-6-174 G/C polymorphism as well as intraocular IL-6 levels among various eye disease patients differ across studies and has not been systematically reviewed. Thus, this study aims to provide a summary to understand the relationship between IL-6 and ophthalmic disease. In total, 8,252 and 11,014 subjects for IL-6-174 G/C and intraocular levels of IL-6, respectively, were retrieved from PubMed, Scopus and Web of Science. No association was found between IL-6-174 G/C polymorphisms with ocular diseases. Subgroup analyses revealed a suggestive association between the GC genotype of IL-6-174 G/C with proliferative diabetic retinopathy (PDR). Further, the level of intraocular IL-6 among ocular disease patients in general was found to be higher than the control group [standardized mean difference (SMD) = 1.41, 95% confidence interval (CI) 1.24–1.58, P < 0.00001]. Closer examination through subgroup analyses yielded similar results in several ocular diseases. This study thus indicates that the IL-6-174 G/C polymorphism does not predispose patients to ocular disease, although the GC genotype is likely to be a genetic biomarker for PDR. Moreover, intraocular IL-6 concentrations are related to the specific manifestations of the ophthalmic diseases. Further studies with larger sample sizes are warranted to confirm this conclusion.


2020 ◽  
Vol 21 (11) ◽  
pp. 3990 ◽  
Author(s):  
Juliana H. Azambuja ◽  
Nils Ludwig ◽  
Saigopalakrishna S. Yerneni ◽  
Elizandra Braganhol ◽  
Theresa L. Whiteside

Interactions between tumor cells and tumor-associated macrophages (TAMs) are critical for glioblastoma progression. The TAMs represent up to 30% of the glioblastoma mass. The role of TAMs in tumor progression and in the mechanisms underlying tumor growth remain unclear. Using an in vitro model resembling the crosstalk between macrophages and glioblastoma cells, we show that glioblastoma-derived exosomes (GBex) reprogram M1 (mediate pro-inflammatory function) and M2 (mediate anti-inflammatory function) macrophages, converting M1 into TAMs and augmenting pro-tumor functions of M2 macrophages. In turn, these GBex-reprogrammed TAMs, produce exosomes decorated by immunosuppressive and tumor-growth promoting proteins. TAM-derived exosomes disseminate these proteins in the tumor microenvironment (TME) promoting tumor cell migration and proliferation. Mechanisms underlying the promotion of glioblastoma growth involved Arginase-1+ exosomes produced by the reprogrammed TAMs. A selective Arginase-1 inhibitor, nor-NOHA reversed growth-promoting effects of Arginase-1 carried by TAM-derived exosomes. The data suggest that GBex-reprogrammed Arginase-1+ TAMs emerge as a major source of exosomes promoting tumor growth and as a potential therapeutic target in glioblastoma.


2021 ◽  
pp. 353-381
Author(s):  
Rania Alhaj Ali ◽  
Hussein Halabi ◽  
Hani Almoallim

AbstractThe prevalence of various cardiovascular diseases (CVD) in the different rheumatologic disorders is a very important topic. Each disease has a number of unique manifestations despite the fact that an overlap is present due to shared common risk factors, which may be related to the longer life expectancy of the recent therapeutic advances. A growing understanding of the role of inflammation and immune system in the initiation and progression of atherosclerosis as well as the early detection of cardiovascular manifestations is due to the availability and use of sophisticated noninvasive cardiac and vascular diagnostic technology. Such discipline results in the detection of cardiac manifestation unique to each rheumatologic disorder. This was not possible previously due to short life expectancy, limited therapeutic interventions, vague understanding of pathological process for each disease, and the limited diagnostic resources.


2021 ◽  
Author(s):  
Yuanyuan Gong ◽  
Zukai Liu ◽  
Yihang Yuan ◽  
Zhenzhen Yang ◽  
Jiawei Zhang ◽  
...  

Abstract PUMILIO (PUM) proteins belong to the highly conserved PUF family post-transcriptional regulators involved in diverse biological processes. However, their function in carcinogenesis remains under explored. Here, we found that the expression of Pum1 and Pum2 are increased in clinical colorectal cancer (CRC). Intestine-specific knockout of Pum1 and Pum2 significantly inhibited the progression of colitis associated cancer in the AOM/DSS model. Knockout or knockdown of Pum1 and/or Pum2 resulted in a significant decrease in the tumorigenicity. In addition, delayed G1/S transition was observed. We identified p21/Cdkn1a as direct target of PUM1, and abrogation of the PUM1 binding site in p21 resulted in decreased tumor cell growth as well as delayed G1/S transition. Furthermore, intravenous injection of nanoparticle-encapsulated anti-Pum1 and Pum2 siRNAs reduced colorectal tumor growth in murine orthotopic colon cancer models. These findings reveal a tumor growth promoting role of PUM proteins in CRC and its potential as therapeutic targets.


2018 ◽  
Vol 5 (2) ◽  
pp. 91-96
Author(s):  
Peng-Fei Han ◽  
Zhi-Liang Zhang ◽  
Tao-Yu Chen ◽  
Rui-Peng Zhao ◽  
Rong Zhang ◽  
...  

Abstract The main pathological change in post-traumatic osteoarthritis (PTOA) is cartilage degeneration, which is closely related to inflammation and oxidative stress. Inflammation can cause degeneration of articular cartilage. Cartilage degeneration can also stimulate the progression of inflammation. It has been found that inflammatory cytokines can participate in the pathological process of cartilage degeneration through multiple signaling pathways, mainly mitogen-activated protein kinase, nuclear transcription factor kappa B, and Wnt–β-catenin signal transduction pathways. This review aimed at exploring the relationship between PTOA and inflammation-related cytokines by introducing the role of proinflammatory cytokines in chondrocyte destruction and extracellular matrix degradation.


1985 ◽  
Vol 63 (4) ◽  
pp. 353-354 ◽  
Author(s):  
C. R. Triggle

The etiology of essential hypertension has been under intensive investigation for a number of years, and the availability of a number of rat models of this disease has aided our understanding of the relationship between abnormalities in cardiovascular regulatory function and hypertension. It is accepted that abnormalities at a number of levels of these regulatory processes could be the basis of the pathological process; however, the cause–effect relationship has not always been clearly established. This introduction addresses the potential relationship between a number of parameters and the control of blood pressure, and the Symposium attempts to relate altered smooth muscle and membrane function to hypertension.


2014 ◽  
Vol 67 (7-8) ◽  
pp. 231-238 ◽  
Author(s):  
Danijela Vucevic ◽  
Tatjana Radosavljevic ◽  
Drago Djordjevic ◽  
Dusan Mladenovic ◽  
Milena Veskovic

Introduction. The etiopathogenesis of atherosclerosis and subsequent pulmonary emphysema has not been fully elucidated. Experimental Studies Foam cells are of great importance in the development of these diseases. It is known that local cytokine secretion and modification of native lipoprotein particles, which are internalized by the vascular and alveolar macrophages via the scavenger receptors on the surfaces of these cells, lead to the formation of foam cells. Thus, the exacerbation of local inflammatory process in the vascular and lung tissue ensues due to a generation of reactive oxygen species, resulting in further lipoprotein modification and cytokine production. Accumulating evidence suggests that oxidants may facilitate the inflammatory response by impairing antiprotease function, directly attacking vascular and lung matrix proteins and by inactivating enzymes involved in elastin synthesis and vascular and lung repair. Clinical Studies Cigarette smoke is recognized as a rich source of oxidants. Nearly 90% of all patients with chronic obstructive pulmonary disease are smokers. The process of atherogenesis is also influenced by tobacco smoke. Conclusion The role of vascular and alveolar macrophages has become increasingly important in understanding the development of atherosclerosis and resulting pulmonary emphysema.


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