scholarly journals Differentially Expressed MicroRNAs Associated with Vein Graft Restenosis in Rats

2020 ◽  
Vol 5 (1) ◽  
pp. 45-55
Author(s):  
Shuwei Wan ◽  
Hui Cao ◽  
Yubo Zhao ◽  
Yaming Guo ◽  
Chuang Li ◽  
...  

Objective: Intimal hyperplasia is the main cause of restenosis of vein grafts after venous transplantation. MicroRNAs are considered to play a role in vein graft restenosis; however, the expression profile of microRNAs in neointima has not been reported in detail. We wanted to investigate the differentially expressed microRNAs in the restenosis of vein grafts in rats.Methods: We established a rat model for vein transplantation to explore the pathogenic roles of microRNAs during intimal hyperplasia. Hematoxylin and eosin staining was used to confirm intimal hyperplasia in the vein grafts. Changes in microRNA expression in the vein grafts were detected 3 and 14 days after surgery by sequencing, reverse transcription‐quantitative polymerase chain reaction, and bioinformatics analyses for functional annotation.Results: We detected 711 newly predicted microRNAs among all the comparisons. Among these comparisons, 437 differentially expressed microRNAs were detected in the postoperative day 3 group versus the control group, 265 were detected in the postoperative day 14 group versus the control group, and 158 were detected in the postoperative day 14 group versus the postoperative day 3 group. Pathway analysis revealed significant enrichment of target genes that mediate Wnt, mitogen-activated protein kinase, vascular smooth muscle contraction, and regulation of actin cytoskeleton signaling.Conclusion: Our results provide insight into the pathogenesis of restenosis and will help develop novel targets in the prevention and treatment of vein graft restenosis.

2017 ◽  
Vol 37 (5) ◽  
Author(s):  
Xiaolin Wu ◽  
Xipeng Chen ◽  
Wenxiang Mi ◽  
Tingting Wu ◽  
Qinhua Gu ◽  
...  

Peri-implantitis, which is characterized by dense inflammatory infiltrates and increased osteoclast activity, can lead to alveolar bone destruction and implantation failure. miRNAs participate in the regulation of various inflammatory diseases, such as periodontitis and osteoporosis. Therefore, the present study aimed to investigate the differential expression of miRNAs in canine peri-implantitis and to explore the functions of their target genes. An miRNA sequence analysis was used to identify differentially expressed miRNAs in peri-implantitis. Under the criteria of a fold-change >1.5 and P<0.01, 8 up-regulated and 30 down-regulated miRNAs were selected for predictions of target genes and their biological functions. Based on the results of Gene Ontology (GO) and KEGG pathway analyses, these miRNAs may fine-tune the inflammatory process in peri-implantitis through an intricate mechanism. The results of quantitative real-time PCR (qRT-PCR) revealed that let-7g, miR-27a, and miR-145 may play important roles in peri-implantitis and are worth further investigation. The results of the present study provide insights into the potential biological effects of the differentially expressed miRNAs, and specific enrichment of target genes involved in the mitogen-activated protein kinase (MAPK) signaling pathway was observed. These findings highlight the intricate and specific roles of miRNAs in inflammation and osteoclastogenesis, both of which are key aspects of peri-implantitis, and thus may contribute to future investigations of the etiology, underlying mechanism, and treatment of peri-implantitis.


2019 ◽  
Vol 119 (12) ◽  
pp. 2014-2024
Author(s):  
Chi-Nan Tseng ◽  
Ya-Ting Chang ◽  
Cih-Yi Yen ◽  
Mariette Lengquist ◽  
Malin Kronqvist ◽  
...  

AbstractInflammatory processes contribute to intimal hyperplasia (IH) and long-term failure of vein grafts used in bypass surgery. Leukocyte recruitment on endothelial cells of vessels during inflammation is regulated by P-selectin and P-selectin glycoprotein ligand-1 (PSGL-1), which also mediates the interaction between platelets and endothelial cells in vein grafts transferred to arteries. However, how this pathway causes IH in vein grafts is unclear. In this study, we used a murine model of vein grafting to investigate P-selectin-mediated platelet adhesion, followed by IH. On the luminal surface of the vein graft, leukocyte recruitment occurred mainly in areas with adhered platelets rather than on endothelial cells without adherent platelets 1 hour after vein grafting. Blockage of either P-selectin or PSGL-1 reduced platelet adhesion and leukocyte recruitment on the luminal surface of vein grafts. Inhibition of the P-selectin pathway in vein grafts significantly reduced platelet-mediated leukocyte recruitment and IH of vein grafts 28 days after surgery. The study demonstrates that functional blockage of the P-selectin/PSGL-1 pathway in the early inflammatory phase after vein grafting reduced leukocyte invasion in the vein graft wall and later IH development. The findings imply an attractive early time window for prevention of vein graft failure by manipulating platelet adhesion.


Animals ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 1417
Author(s):  
Chuan Li ◽  
Ting Xiong ◽  
Mingfang Zhou ◽  
Lei Wan ◽  
Suwang Xi ◽  
...  

Poultry skeletal muscle provides high quality protein for humans. Study of the genetic mechanisms during duck skeletal muscle development contribute to future duck breeding and meat production. In the current study, three breast muscle samples from Shan Ma ducks at embryonic day 13 (E13) and E19 were collected, respectively. We detected microRNA (miRNA) expression using high throughput sequencing following bioinformatic analysis. qRT-PCR validated the reliability of sequencing results. We also identified target prediction results using the luciferase reporter assay. A total of 812 known miRNAs and 279 novel miRNAs were detected in six samples; as a result, 61 up-regulated and 48 down-regulated differentially expressed miRNAs were identified between E13 and E19 (|log2 fold change| ≥ 1 and p ≤ 0.05). Enrichment analysis showed that target genes of the differentially expressed miRNAs were enriched on many muscle development-related gene ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, especially mitogen-activated protein kinase (MAPK) signaling pathways. An interaction network was constructed using the target genes of the differentially expressed miRNAs. These results complement the current duck miRNA database and offer several miRNA candidates for future studies of skeletal muscle development in the duck.


Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1173 ◽  
Author(s):  
Mailin Gan ◽  
Shunhua Zhang ◽  
Yuan Fan ◽  
Ya Tan ◽  
Zhixian Guo ◽  
...  

Cardiac hypertrophy is a common pathological condition and an independent risk factor that triggers cardiovascular morbidity. As an important epigenetic regulator, miRNA is widely involved in many biological processes. In this study, miRNAs expressed in rat hearts that underwent isoprenaline-induced cardiac hypertrophy were identified using high-throughput sequencing, and functional verification of typical miRNAs was performed using rat primary cardiomyocytes. A total of 623 miRNAs were identified, of which 33 were specifically expressed in cardiac hypertrophy rats. The enriched pathways of target genes of differentially expressed miRNAs included the FoxO signaling pathway, dopaminergic synapse, Wnt signaling pathway, MAPK (mitogen-activated protein kinase) signaling pathway, and Hippo signaling pathway. Subsequently, miR-144 was the most differentially expressed miRNA and was subsequently selected for in vitro validation. Inhibition of miR-144 expression in primary myocardial cells caused up-regulation of cardiac hypertrophy markers atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). The dual luciferase reporter system showed that ANP may be a target gene of miR-144. Long non-coding RNA myocardial infarction associated transcript (LncMIAT) is closely related to heart disease, and here, we were the first to discover that LncMIAT may act as an miR-144 sponge in isoproterenol-induced cardiac hypertrophy. Taken together, these results enriched the understanding of miRNA in regulating cardiac hypertrophy and provided a reference for preventing and treating cardiac hypertrophy.


2021 ◽  
Vol 12 ◽  
Author(s):  
Si Ying Li ◽  
Chen Yi Wang ◽  
Yun Xia Xiao ◽  
Xiao Bing Tang ◽  
Zheng Wei Yuan ◽  
...  

Anorectal malformations (ARMs) are among the most common congenital terminal digestive tract malformations. Circular RNAs (circRNAs), a novel type of endogenous non-coding RNAs, play roles in the development of the digestive system; however, their contributions to the pathogenesis of ARMs are not well-established. In this study, we explored the mechanism underlying ethylenethiourea (ETU)-induced ARMs by profiling circRNA expression via RNA-seq and constructing a regulatory circRNA-miRNA-mRNA network. Nine pregnant rats were gavage-fed a single dose of 125 mg/kg 1% ETU (ARM group) on gestational day 10 (GD10), and another 9 pregnant rats received a similar dose of saline (normal group) as a control. Embryos were obtained by cesarean section on the key time-points of anorectal development (GD14, GD15, and GD16). Hindgut samples isolated from the fetuses were evaluated by high-throughput sequencing and differentially expressed circRNAs were validated by reverse transcription-quantitative polymerase chain reaction, agarose gel electrophoresis, and Sanger cloning and sequencing. A total of 18295 circRNAs were identified in the normal and ARM groups. Based on the 425 differentially expressed circRNAs (|Fc| &gt; 2, p &lt; 0.05), circRNA-miRNA and miRNA-mRNA pairs were predicted using miREAP, miRanda, and TargetScan. A total of 55 circRNAs (14 up- and 41 downregulated in the ARM group compared to the normal group) were predicted to bind to 195 miRNAs and 947 mRNAs. Competing endogenous RNA networks and a Kyoto Encyclopedia of Genes and Genomes analysis revealed that novel_circ_001042 had the greatest connectivity and was closely related to ARM-associated signaling pathways, such as the Wingless Type MMTV integration site family, mitogen-activated protein kinase, and transforming growth factor-β pathways. These results provide original insight into the roles of circRNAs in ARMs and provide a valuable resource for further analyses of molecular mechanisms and signaling networks.


Genome ◽  
2021 ◽  
Author(s):  
Ying Luo ◽  
Tao Wang ◽  
Dan Yang ◽  
Biao Luo ◽  
Weiping Wang ◽  
...  

Abstract: MicroRNAs (miRNAs) are small, non-coding, regulatory RNAs that play important roles in abiotic stress responses in plants. but their regulatory roles in the adaptive response to heat stress at the booting stage in two rice varieties 9311 and Nagina 22, remain largely unknown. In this study, 464 known miRNAs and 123 potential novel miRNAs were identified. Of these miRNAs, a total of 90 differential expressed miRNAs were obtained with 9311 libraries as control group, of which 54 upregulated and 36 downregulated miRNAs. To gain insight into functional significance, 2773 potential target genes of these 90 differentially expressed miRNAs were predicted. GO enrichment showed that the predicted target genes of differentially expressed miRNAs including NACs, LACs, CSD, and Hsp40. KEGG pathway analysis showed that target genes of these differentially expressed miRNAs were significantly enriched in plant hormone signal transduction pathway. The expression levels of ten differentially expressed miRNAs and their target genes obtained by qRT-PCR were largely consistent with the sequencing results. This study lays a foundation for the elucidation of the miRNA-mediated regulatory mechanism in rice at elevated temperatures. Key words: rice, heat-responsive, microRNA, target gene, booting stage, high-throughput sequencing


2020 ◽  
Author(s):  
Pei Yu ◽  
Wencheng Chen

Abstract Background Erythrocyte deformability is one of the pathophysiological changes of high-risk factors such as smoking, hypertension and atherosclerosis in stroke. It mainly affects blood viscosity and fluidity in the occurrence, development and outcome of the disease. Exosomes are a new type of biological activity test target, and it mainly contents miRNA, but its effect on stroke is still not clear. Objective To detect the serum exosome-derived miR-150-5p expression in patients with acute ischemic stroke and explore its diagnostic potential for acute ischemic stroke. Methods A total of 84 samples were collected with matched age and gender, collecting relevant laboratory indicators and general clinical data of the research subjects. The kit was used to extract serum exosomes, real-time fluorescent quantitative polymerase chain reaction was used to determine the expression of serum exosomal miR-150-5p, evaluate its value as a diagnostic marker through the ROC curve. Through Randa, Target Scan and other online databases, bioinformatics methods predict the target genes of miR-150, the results are drawn Venny to take intersection analysis, literature screening and ischemic stroke related target genes. Results The exosomes showed elliptical or round membranous vesicles with a diameter between 30–200 nm and fusion phenomenon and detected the exosomal marker proteins CD63 and HSP70; Compared with the control group, the relative expression of exosomal miR-150-5p in patients with acute ischemic stroke was increased (T = 8, P < 0.001). The expression of serum exosomal miR-150-5p in the disease group at different time points after stroke, the difference was not statistically significant(Chi-square = 2.925, P = 0.232); the area under the ROC curve was 0.883. bioinformatics prediction analysis of miR-150 target genes, which may be involved in the development of stroke disease through EGR2 and PLP2, as well as erythrocyte membrane protein-related genes SLC4A1 and SPTB also belong to the miR-150 prediction targets. Conclusion The expression of exosome-derived miR-150-5p is relatively high in patients with acute stroke, and it has a certain potential for early disease diagnosis.


2020 ◽  
Author(s):  
Qing Xia ◽  
Qiuling Li ◽  
Shangquan Gan ◽  
Xiaofei Guo ◽  
Xiaosheng Zhang ◽  
...  

Abstract Background Long non-coding RNAs (lncRNAs) can play important roles in uterine and ovarian functions. However, little researches have been done on the role of lncRNAs in the adrenal gland of sheep. Herein, RNA sequencing was used to compare and analyze gene expressions in adrenal tissues between FecB ++ (WW) and FecB BB (MM) sheep in the follicular and luteal phases and key lncRNAs and genes associated with reproduction were identified. Results In MM sheep, 38 lncRNAs and 545 mRNAs were differentially expressed in the adrenal gland between the luteal and follicular phases; In WW sheep, 30 differentially expressed lncRNAs and 210 mRNAs were identified. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses indicated that differentially expressed lncRNAs and their target genes are mainly involved in the circadian rhythm, the mitogen activated protein kinase, thyroid, ovarian steroidogenesis and transforming growth factor beta signaling pathways. Key lncRNAs can regulate reproduction by modulating genes involved in these signaling pathways and biological processes. Specifically, XLOC_254761 , XLOC_357966 , 105614839 and XLOC_212877 targeting CREB1 , PER3 , SMAD1 and TGFBR2 , respectively, appear to play key regulatory roles. Conclusion These results broaden our understanding of lncRNAs in adrenal gland of sheep and provide new insights into the molecular mechanisms underlying sheep reproduction.


2020 ◽  
Author(s):  
Shi Wu ◽  
Dan Lu ◽  
Xinkai Zheng ◽  
Jin Xu ◽  
Zhen Li ◽  
...  

Abstract Objectives This study was designed to investigate the miRNAs that regulate the cell proliferation of condyloma acuminatum (CA) lesions and their targets.Methods The expression of Ki-67 in 26 CA patients compared with 10 healthy controls was assessed by immunohistochemistry. And the different miRNAs in 4 CA patients and 4 control cases were analyzed by bioinformatics. PCR was used to validate the expression of screened miRNA and its corresponding target genes.Results The expression of Ki-67 was abnormally increased in CA compared with healthy controls ( P <0.05). The comparison of the control group with the CA group revealed 81 differentially expressed miRNAs, of which 56 were downregulated and 25 were upregulated. Two of the differentially expressed miRNAs, miR-30a-5p and miR-514a-3p, are associated with cell proliferation and their target genes are autophagy-related protein (Atg) 5 and Atg12, and Atg3 and Atg12, respectively. PCR results showed that the expression levels of miR-30a-5p and miR-514a-3p were decreased in CA patients compared with healthy controls ( P <0.05), whereas the expression of Atg5, Atg12 and Atg3 was increased ( P <0.05). The expression of the autophagy proteins microtubule-associated protein 1 light chain 3 (LC3) and P62/SQSTM1 (P62) was abnormally increased in the local lesion tissue of the 26 patients with CA compared with the 10 healthy controls, as assessed by immunohistochemistry ( P <0.05).Conclusions Our results suggest that autophagy levels may be modulated by has-miRNA30a-5p and has-miRNA514a-3p in CA patients, leading to dysregulated cell proliferation.


BMC Genomics ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Shaoyang Ma ◽  
Chao Tong ◽  
Eveline M. Ibeagha-Awemu ◽  
Xin Zhao

Abstract Background MicroRNAs (miRNAs) in milk-derived exosomes may reflect pathophysiological changes caused by mastitis. This study profiled miRNAs in exosomes from both normal milk and mastitic milk infected by Staphylococcus aureus (S. aureus). The potential targets for differentially expressed (DE) miRNAs were predicted and the target genes for bta-miR-378 and bta-miR-185 were also validated. Results Total RNA from milk exosomes was collected from healthy cows (n = 3, the control group) and S. aureus infected cows (n = 6, the SA group). Two hundred ninety miRNAs (221 known and 69 novel ones) were identified. Among them, 22 known and 15 novel miRNAs were differentially expressed. Target genes of DE miRNAs were significantly enriched in intracellular protein transport, endoplasmic reticulum and identical protein binding. The expression of two miRNAs (bta-miR-378 and bta-miR-185) with high read counts and log2 fold changes (> 3.5) was significantly higher in mastitic milk infected with S. aureus. One target gene (VAT1L) of bta-miR-378 and five target genes (DYRK1B, MLLT3, HP1BP3, NPR2 and PGM1) of bta-miR-185 were validated. Conclusion DE miRNAs in exosomes from normal and S. aureus infected milk were identified. The predicted targets for two DE miRNAs (bta-miR-378 and bta-miR-185) were further validated. The linkage between the validated target genes and diseases suggested that we should pay particular attention to exosome miRNAs from mastitic milk in terms of milk safety.


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