Characterization of Long Noncoding RNA and mRNA Profiles in Sepsis-Induced Myocardial Depression

Zhang, Tie-Ning; Goodwin, Julie E.; Liu, Bing; Li, Da; Wen, Ri; Yang, Ni; Xia, Jing; Zhou, Han; Zhang, Tao; Song, Wu; Liu, Chunfeng

doi:10.1016/j.omtn.2019.07.020

Cited by 36 publications

(89 citation statements)

References 27 publications

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“…As mentioned previously [ 2 , 12 ], our group has found that there is a positive relationship between the MAP and heart function. In this study, septic shock occurred at approximately 2 hours after LPS injection, and the MAP of the control groups remained unchanged ( Figure 1(a) ).…”

Section: Resultssupporting

confidence: 72%

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Overexpression of miR-150-5p Alleviates Apoptosis in Sepsis-Induced Myocardial Depression

Zhu

Zhang

Wen

et al. 2020

BioMed Research International

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Sepsis-induced myocardial depression has high mortality and is very common in intensive care units. Previous studies have found that microRNAs play an important role in regulating sepsis-induced myocardial depression. miR-150-5p is involved in many biological processes; however, the mechanism underlying its role in sepsis-induced myocardial depression is still unclear. In this study, we generated rat models of septic shock induced by lipopolysaccharide. Whole genomic RNA sequencing was performed on 12 left ventricles collected after LPS treatment to identify miRNAs. Most of the target genes of the differently expressed microRNAs were involved in apoptosis, according to Gene Ontology. We also observed apoptosis in the heart tissue and in H9C2 cardiomyocytes stimulated with lipopolysaccharide, indicating that cell apoptosis may be an important mechanism in sepsis-induced myocardial depression. Furthermore, the expression of miR-150-5p was reduced, and overexpression of miR-150-5p with mimics resulted in a decrease in apoptosis, decreased expression of cleaved caspase3 and Bax, and increased expression of Bcl-2. Additionally, after H9C2 cells were transfected with miR-150-5p mimics or an inhibitor, the expression of Akt2 decreased or increased, respectively. These findings suggest that miR-150-5p can alleviate apoptosis and may be a novel therapeutic target for sepsis-induced myocardial depression.

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Section: Resultssupporting

confidence: 72%

“…Based on the sequencing results described previously [ 9 , 12 ], we selected certain microRNAs for further analysis. The target genes of the differently expressed miRNAs were identified using the miRanda, PITA, and RNAhybrid databases [ 13 – 15 ].…”

Section: Methodsmentioning

confidence: 99%

Overexpression of miR-150-5p Alleviates Apoptosis in Sepsis-Induced Myocardial Depression

Zhu

Zhang

Wen

et al. 2020

BioMed Research International

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“…Several long non-coding RNAs (lncRNAs) (data not shown), were also significantly regulated in the septic heart samples. Such lncRNAs are in a rat model, suggested play an interaction and regulation role in the pathogenesis of sepsis-induced myocardial depression (Zhang T. N. et al, 2019).…”

Section: Transcriptional Profiles In Heart Tissue Samplesmentioning

confidence: 99%

Extensive Changes in Transcriptomic “Fingerprints” and Immunological Cells in the Large Organs of Patients Dying of Acute Septic Shock and Multiple Organ Failure Caused by Neisseria meningitidis

Brusletto

Løberg

Hellerud

et al. 2020

Front. Cell. Infect. Microbiol.

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Background: Patients developing meningococcal septic shock reveal levels of Neisseria meningitidis (10 6-10 8 /mL) and endotoxin (10 1-10 3 EU/mL) in the circulation and organs, leading to acute cardiovascular, pulmonary and renal failure, coagulopathy and a high case fatality rate within 24 h. Objective: To investigate transcriptional profiles in heart, lungs, kidneys, liver, and spleen and immunostain key inflammatory cells and proteins in post mortem formalin-fixed, paraffin-embedded (FFPE) tissue samples from meningococcal septic shock patients. Patients and Methods: Total RNA was isolated from FFPE and fresh frozen (FF) tissue samples from five patients and two controls (acute non-infectious death). Differential expression of genes was detected using Affymetrix microarray analysis. Lung and heart tissue samples were immunostained for T-and B cells, macrophages, neutrophils and the inflammatory markers PAI-1 and MCP-1. Inflammatory mediators were quantified in lysates from FF tissues. Results: The transcriptional profiles showed a complex pattern of protein-coding and non-coding RNAs with significant regulation of pathways associated with organismal death, cell death and survival, leukocyte migration, cellular movement, proliferation of cells, cell-to-cell signaling, immune cell trafficking, and inflammatory responses in an organ-specific clustering manner. The canonical pathways including acute phase response-, EIF2-, TREM1-, IL-6-, HMBG1-, PPAR signaling, and LXR/RXR activation were associated with acute heart, pulmonary, and renal failure. Fewer genes were regulated in the liver and particularly in the spleen. The main upstream regulators were TNF, IL-1β, IL-6, RICTOR, miR-6739-3p, and CD3. Increased numbers of inflammatory cells (CD68+, MPO+, CD3+, and CD20+) were found in lungs and heart. PAI-1 inhibiting Brusletto et al. Transcriptional Profiles in MSS Organs fibrinolysis and MCP-1 attracting leukocyte were found significantly present in the septic tissue samples compared to the controls. Conclusions: FFPE tissue samples can be suitable for gene expression studies as well as immunostaining of specific cells or molecules. The most pronounced gene expression patterns were found in the organs with highest levels of Neisseria meningitidis DNA. Thousands of protein-coding and non-coding RNA transcripts were altered in lungs, heart and kidneys. We identified specific biomarker panels both protein-coding and non-coding RNA transcripts, which differed from organ to organ. Involvement of many genes and pathways add up and the combined effect induce organ failure.

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“…Long noncoding RNAs (lncRNAs) are a class of RNA that are longer than 200 nucleotides, and with no protein-coding potential [8]. They modulate gene expression at different levels, including chromosome reconstruction, transcription, and post-transcription [9]. LncRNAs play various critical biological functions such as acting as signaling, decoy, guide, and scaffold molecules [10].…”

Section: Ivyspringmentioning

confidence: 99%

Down-regulation of Xist and Mir-7a-5p improves LPS-induced myocardial injury

Liang¹,

Jin²,

Lin³

et al. 2020

Int. J. Med. Sci.

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Background: X-inactive specific transcript (Xist) is a lncRNA, which plays a significant role in X-chromosome inactivation, regulates cell proliferation in tumor cells, and inhibits apoptosis in acute myocardial infarction. On the other hand, miR-7a-5p is involved in cardiomyocytes injury in myocardial ischemia/reperfusion. However, their roles in LPS-induced damage remain unclear. Objectives: This study aimed at using siRNA transfection and lentivirus infection to regulate the expression of xist and miR-7a-5p, and to evaluate their effects on LPS-induced myocardial damage. Method: Mice cardiomyocytes (MCM) cells were divided into six groups, namely the control group, the LPS group, the LPS + lncRNAgroup, the LPS + lncRNA + group, the LPS + miRNAgroup, and the LPS + miRNA + group. Quantitative real-time PCR (qRT-PCR) was performed to assay for the RNA expressions of xist, miR-7a-5p, peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), and recombinant mitochondrial transcription factor A (Tfam) in all the groups. The ATP level was determined using the adenosine triphosphate (ATP) assay kit according to the manufacturer's instructions. Flow cytometry was performed to estimate the level of apoptosis and proliferation in cells in each group. Results: The level of xist in the myocardial cells was markedly higher in the LPS group compared with the control group; however, it was reduced in the LPS+ lncRNAgroup. There was no significant difference in the expression of xist among the LPS+miRNA-, LPS+miRNA + , and LPS groups. Moreover, the expression of mir-7a-5p was significantly reduced in myocardial cells in the LPS group, and moderately reduced in the LPS+ miRNAgroup, but remarkably elevated in the LPS+ miRNA + group (P<0.05). The expression of mir-7a-5p was comparably similar in the LPS+ lncRNAgroup, LPS+ lncRNA + group, and LPS groups. Further, the levels of PGC-1a, and Tfam were determined. In the LPS group, the expression of PGC-1α was significantly reduced but elevated in the LPS+lncRNA-and LPS+ miRNAgroups (P<0.05). There was no significant difference in the level of PGC-1α among the LPS, LPS+ lncRNA + , and LPS+ miRNA + groups. The expression of Tfam was markedly reduced in the LPS group (P < 0.05), but elevated after the suppression of xist and mir-7a-5p. The expression of Tfam was not significantly different among the LPS group, LPS+ lncRNA + and LPS+ miRNA + groups. Notably, overexpression of mir-7a-5p had a mild effect on the expression of Tfam in the LPS+ miRNA + group compared with the control group. Besides, ATP expression in the LPS group was markedly reduced, but elevated after the inhibition of xist and mir-7a-5p. Suppressing the expression of xist or mir-7a-5p resulted in reduced cell apoptosis and increased cell proliferation. Conclusions: In this study, we established that down-regulation of xist and mir-7a-5p reduces apoptosis in response to LPS.

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Characterization of Long Noncoding RNA and mRNA Profiles in Sepsis-Induced Myocardial Depression

Cited by 36 publications

References 27 publications

Overexpression of miR-150-5p Alleviates Apoptosis in Sepsis-Induced Myocardial Depression

Overexpression of miR-150-5p Alleviates Apoptosis in Sepsis-Induced Myocardial Depression

Extensive Changes in Transcriptomic “Fingerprints” and Immunological Cells in the Large Organs of Patients Dying of Acute Septic Shock and Multiple Organ Failure Caused by Neisseria meningitidis

Down-regulation of Xist and Mir-7a-5p improves LPS-induced myocardial injury

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