scholarly journals Full-length transcriptome analysis reveals the mechanism of acupuncture at PC6 improves cardiac function in myocardial ischemia model

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Jing Yuan ◽  
Jun-Meng Wang ◽  
Zhi-Wei Li ◽  
Cheng-Shun Zhang ◽  
Bin Cheng ◽  
...  

Abstract Background The pathological process of myocardial ischemia (MI) is very complicated. Acupuncture at PC6 has been proved to be effective against MI injury, but the mechanism remains unclear. This study investigated the mechanism that underlies the effect of acupuncture on MI through full-length transcriptome. Methods Adult male C57/BL6 mice were randomly divided into control, MI, and PC6 groups. Mice in MI and PC6 group generated MI model by ligating the left anterior descending (LAD) coronary artery. The samples were collected 5 days after acupuncture treatment. Results The results showed that treatment by acupuncture improved cardiac function, decreased myocardial infraction area, and reduced the levels of cTnT and cTnI. Based on full-length transcriptome sequencing, 5083 differential expression genes (DEGs) and 324 DEGs were identified in the MI group and PC6 group, respectively. These genes regulated by acupuncture were mainly enriched in the inflammatory response pathway. Alternative splicing (AS) is a post-transcriptional action that contributes to the diversity of protein. In all samples, 8237 AS events associated with 1994 genes were found. Some differential AS-involved genes were enriched in the pathway related to heart disease. We also identified 602 new genes, 4 of which may the novel targets of acupuncture in MI. Conclusions Our findings suggest that the effect of acupuncture on MI may be based on the multi-level regulation of the transcriptome.

Author(s):  
Carina Henning ◽  
Anna Branopolski ◽  
Paula Follert ◽  
Oksana Lewandowska ◽  
Aysel Ayhan ◽  
...  

Abstract Background Short episodes of myocardial ischemia can protect from myocardial infarction. However, the role of endothelial β1 integrin in these cardioprotective ischemic events is largely unknown. Objective In this study we investigated whether endothelial β1 integrin is required for cardiac adaptation to ischemia and protection from myocardial infarction. Methods Here we introduced transient and permanent left anterior descending artery (LAD) occlusions in mice. We inhibited β1 integrin by intravenous injection of function-blocking antibodies and tamoxifen-induced endothelial cell (EC)-specific deletion of Itgb1. Furthermore, human ITGB1 was silenced in primary human coronary artery ECs using small interfering RNA. We analyzed the numbers of proliferating ECs and arterioles by immunohistochemistry, determined infarct size by magnetic resonance imaging (MRI) and triphenyl tetrazolium chloride staining, and analyzed cardiac function by MRI and echocardiography. Results Transient LAD occlusions were found to increase EC proliferation and arteriole formation in the entire myocardium. These effects required β1 integrin on ECs, except for arteriole formation in the ischemic part of the myocardium. Furthermore, this integrin subunit was also relevant for basal and mechanically induced proliferation of human coronary artery ECs. Notably, β1 integrin was needed for cardioprotection induced by transient LAD occlusions, and the absence of endothelial β1 integrin resulted in impaired growth of blood vessels into the infarcted myocardium and reduced cardiac function after permanent LAD occlusion. Conclusion We showed that endothelial β1 integrin is required for adaptation of the heart to cardiac ischemia and protection from myocardial infarction.


Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 254
Author(s):  
Zi-Hao Wang ◽  
Fei Ke ◽  
Qi-Ya Zhang ◽  
Jian-Fang Gui

Carassius auratus herpesvirus (CaHV) has been identified as a high-virulence pathogenic virus that infects aquatic animals, but the key factor for virus–host interaction is still unclear. Five Really interesting new genes (RING) finger proteins (39L, 52L, 131R, 136L, and 143R) of CaHV were screened to determine structural diversity. RING finger proteins were also predicted in other known fish herpesviruses, with an arrangement and number similar to CaHV. We performed multifaceted analyses of the proteins, including protein sizes, skeleton structures, subcellular localizations, and ubiquitination activities, to determine their precise roles in virus–host interactions. The five proteins were overexpressed and detected different levels of ubiquitination activities, and 143R showed the highest activity. Then, the prokaryotic expressed and purified full-length proteins (131R and 136L), RING domain isolates (131R12–43 and 136L45–87), and RING domain-deleted mutants (131RΔ12–43 and 136LΔ45–87) were prepared to detect their activities through ubiquitination assays. The results indicate that both full-length proteins and their isolates have activities that catalyze ubiquitination, and the full-length proteins possess higher activity than the isolates, but RING domain-deleted mutants lose their activities. Furthermore, the activities of the five proteins were verified as E3 ubiquitin ligase activity, showing that the RING domains determine the ubiquitination activity. These proteins present different subcellular localization. RING domain-deleted mutants showed similar subcellular localization with their full-length proteins, and all the isolates diffused in whole cells. The current results indicate that the sequence outside the RING domain determines subcellular localization and the level of ubiquitination activity, suggesting that the RING finger proteins of fish herpesviruses might have diverse functions in virus–host interaction.


2018 ◽  
Vol 49 (4) ◽  
pp. 1476-1491 ◽  
Author(s):  
Shu-Bo  Zhang ◽  
Tie-Jun Liu ◽  
Guo-Hua Pu ◽  
Bao-Yong Li ◽  
Xiao-Zeng Gao ◽  
...  

Background/Aims: Long non-coding RNA (lncRNA) and glucagon-like peptide 1 receptor (GLP-1R) are crucial for heart development and for adult heart structural maintenance and function. Herein, we performed a study to explore the effect of lncRNA LINC00652 (LINC00652) on myocardial ischemia-reperfusion (I/R) injury by targeting GLP-1R through the cyclic adenosine monophosphate-protein kinase A (cAMP/PKA) pathway. Methods: Bioinformatics software was used to screen the long-chain non-coding RNAs associated with myocardial ischemia-reperfusion and to predict target genes. The mRNA and protein levels of LINC00652, GLP-1R and CREB were detected by RT-qPCR and western blotting. In order to identify the interaction between LINC00652 and myocardial I/R injury, the cardiac function, the hemodynamic changes, the pathological changes of the myocardial tissues, the myocardial infarct size, and the apoptosis of myocardial cells of mice were measured. Meanwhile, the levels of serum IL-1β and TNF-α were detected. Results: LINC00652 was overexpressed in the myocardial cells of mice with myocardial I/R injury. GLP-1R is the target gene of LINC00652. We also determined higher levels of LINC00652 and GLP-1R in the I/R modeled mice. Additionally, si-LINC00652 decreased cardiac pathology, infarct size, apoptosis rates of myocardial cells, and levels of IL-1β and TNF-α, and increased GLP-1R expression cardiac function, normal hemodynamic index, and the expression and phosphorylation of GLP-1R and CREB proteins. Conclusion: Taken together, our key findings of the present highlight LINC00652 inhibits the activation of the cAMP/PKA pathway by targeting GLP-1R to reduce the protective effect of sevoflurane on myocardial I/R injury in mice.


Author(s):  
Wei Li ◽  
Lufeng Fu ◽  
Ziwen Geng ◽  
Xiaojuan Zhao ◽  
Qinghua Liu ◽  
...  

Abstract Rose (Rosa chinensis) is the most important ornamental crops worldwide. However, the physiological and molecular mechanism of rose under drought stress remains elusive. In this study, we analyzed the changes of photosynthetic and phytohormone levels in the leaves and roots of rose seedlings grown under control (no drought/ND), mild (MD), and severe (SD) drought stress. The total chlorophyll content and water use efficiency were significantly enhanced under MD in rose leaves. In addition, the concentration of abscisic acid (ABA) was higher in the leaves compared to the roots, whereas the roots accumulated more indole-3-acetic acid (IAA), methylindole-3-acetic acid (Me-IAA) and indole-3-propionic acid (IPA). We also constructed the first full-length transcriptome for rose, and identified 96,201,862 full-length reads of average length 1,149 bp that included 65,789 novel transcripts. A total of 3,657 and 4,341 differentially expressed genes (DEGs) were identified in rose leaves and roots respectively. KEGG pathway analysis showed enrichment of plant hormone, signal transduction, and photosynthesis are among the DEGs. 42,544 alternatively spliced isoforms were also identified, and alternative 3ʹ splice site was the major alternative splicing (AS) event among the DEGs. Variations in the AS patterns of three genes between leaves and roots indicated the possibility of tissue-specific posttranscriptional regulation in response to drought stress. Furthermore, 2,410 novel long non-coding RNAs were detected that may participate in regulating the drought-induced DEGs. Our findings identified previously unknown splice sites and new genes in the rose transcriptome, and elucidated the drought stress-responsive genes as well as their intricate regulatory networks.


2018 ◽  
Vol 234 (5) ◽  
pp. 5488-5495 ◽  
Author(s):  
Yitian Zheng ◽  
Binhao Shi ◽  
Mengqing Ma ◽  
Xiaoqin Wu ◽  
Xianhe Lin

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Annika Öhrfelt ◽  
Julien Dumurgier ◽  
Henrik Zetterberg ◽  
Agathe Vrillon ◽  
Nicholas J. Ashton ◽  
...  

Abstract Background Neurogranin (Ng) is a neuron-specific and postsynaptic protein that is abundantly expressed in the brain, particularly in the dendritic spine of the hippocampus and cerebral cortex. The enzymatic cleavage of Ng produces fragments that are released into cerebrospinal (CSF), which have been shown to be elevated in Alzheimer’s disease (AD) patients and predict cognitive decline. Thus, quantification of distinctive cleavage products of Ng could elucidate different features of the disease. Methods In this study, we developed novel ultrasensitive single molecule array (Simoa) assays for measurement of full-length neurogranin (FL-Ng) and C-terminal neurogranin (CT-Ng) fragments in CSF. The Ng Simoa assays were evaluated in CSF samples from AD patients (N = 23), mild cognitive impairment due to AD (MCI-AD) (N = 18), and from neurological controls (N = 26). Results The intra-assay repeatability and inter-assay precision of the novel methods had coefficients of variation below 7% and 14%, respectively. CSF FL-Ng and CSF CT-Ng median concentrations were increased in AD patients (6.02 ng/L, P < 0.00001 and 452 ng/L, P = 0.00001, respectively) and in patients with MCI-AD (5.69 ng/L, P < 0.00001 and 566 ng/L, P < 0.00001) compared to neurological controls (0.644 ng/L and 145 ng/L). The median CSF ratio of CT-Ng/FL-Ng were decreased in AD patients (ratio = 101, P = 0.008) and in patients with MCI-AD (ratio = 115, P = 0.016) compared to neurological controls (ratio = 180). CSF of FL-Ng, CT-Ng, and ratio of CT-Ng/FL-Ng could each significantly differentiate AD patients from controls (FL-Ng, AUC = 0.907; CT-Ng, AUC = 0.913; CT-Ng/FL-Ng, AUC = 0.775) and patients with MCI-AD from controls (FL-Ng, AUC = 0.937; CT-Ng, AUC = 0.963; CT-Ng/FL-Ng, AUC = 0.785). Conclusions Assessments of the FL-Ng and CT-Ng levels in CSF with the novel sensitive immunoassays provide a high separation of AD from controls, even in early phase of the disease. The novel Ng assays are robust and highly sensitive and may be valuable tools to study synaptic alteration in AD, as well as to monitor the effect on synaptic integrity of novel drug candidates in clinical trials.


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