Identification of stably expressed housekeeping miRNAs in endothelial cells and macrophages in an inflammatory setting

Link, Fabian; Krohn, Knut; Schümann, Julia

doi:10.1038/s41598-019-49241-7

Cited by 14 publications

(9 citation statements)

References 42 publications

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“…Similarly, mir-30b had a near 3-fold increase (P < 0.05). However, the levels of mir-127 (98), mir-451, and mir-92a were stable between mock ECExos and R -ECExos ( Fig. 5c ).…”

Section: Resultsmentioning

confidence: 94%

Endothelial exosome plays functional role during rickettsial infection

Liu

Zhou

et al. 2020

Preprint

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Spotted fever group rickettsioses (SFRs) are devastating human infections. Vascular endothelial cells (ECs) are the primary targets of infection. Edema resulting from EC barrier dysfunction occurs in the brain and lungs in most cases of lethal SFR, but the underlying mechanisms remain unclear. The aim of the study is to explore the potential role of Rickettsia (R)-infected, EC-derived exosomes (Exos) during infection. Using size-exclusion chromatography (SEC), we purified Exos from conditioned, filtered, bacteria-free media collected from R-infected human umbilical vein ECs (HUVECs) (R-ECExos) and plasma of R-infected mice (R-plsExos). We observed that rickettsial infection increases the release of heterogeneous plsExos, but endothelial exosomal size, morphology, and production were not significantly altered following infection. Compared to normal plsExos and ECExos, both R-plsExos and R-ECExos induced dysfunction of recipient normal brain microvascular Ecs (BMECs). The effect of R-plsExos on mouse recipient BMEC barrier function is dose-dependent. The effect of R-ECExos on human recipient BMEC barrier function is dependent on exosomal RNA cargo. Next-generation sequencing analysis and stem-loop quantitative reverse transcription PCR (RT-qPCR) validation revealed that R infection triggered the selective enrichment of endothelial exosomal mir-23a and mir-30b, which target the endothelial barrier. To our knowledge, this is the first report on the functional role of extracellular vesicles following infection by obligately intracellular bacteria.ImportanceSpotted fever group rickettsioses are devastating human infections. Vascular endothelial cells are the primary targets of infection. Edema resulting from endothelial barrier dysfunction occurs in the brain and lungs in most cases of lethal rickettsioses, but the underlying mechanisms remain unclear. The aim of the study is to explore the potential role of Rickettsia-infected, endothelial cell-derived exosomes during infection. We observed that rickettsial infection increases the release of heterogeneous plasma Exos, but endothelial exosomal size, morphology, and production were not significantly altered following infection. Rickettsia-infected, endothelial cell-derived exosomes induced dysfunction of recipient normal brain microvascular endothelial cells. The effect is dependent on exosomal RNA cargo. Next-generation sequencing analysis revealed that rickettsial infection triggered the selective enrichment of endothelial exosomal mir-23a and mir-30b, which target the endothelial barrier. To our knowledge, this is the first report on the functional role of extracellular vesicles following infection by obligately intracellular bacteria.

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“…Similarly, mir-30b had a near 3-fold increase (P < 0.05). However, the levels of mir-127 (98), mir-451, and mir-92a were stable between mock ECExos and R -ECExos ( Fig. 5c ).…”

Section: Resultsmentioning

confidence: 94%

Endothelial exosome plays functional role during rickettsial infection

Liu

Zhou

et al. 2020

Preprint

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“…For instance, a previous study suggested that miR-151a-5p could be involved in the regulation of cell respiration and ATP production in mitochondria via targeting cytochrome B ( 18 ). As a member of housekeeping miRNAs, miR-151a-5p was identified to be stably expressed in endothelial cells and macrophages in an inflammatory setting ( 19 ). Furthermore, Guo et al ( 20 ) showed that miR-151a-5p was upregulated in lung cancer, while miR-151a-5p silencing could inhibit the proliferation, invasion and migration, and induce the apoptosis of A549 lung cancer cells.…”

Section: Introductionmentioning

confidence: 99%

miR‑151a‑5p promotes the proliferation and metastasis of colorectal carcinoma cells by targeting AGMAT

et al. 2023

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Colorectal carcinoma (CRC) is one of the most common types of digestive cancer. It has been reported that the ectopic expression of microRNAs (miRs) plays a critical role in the occurrence and progression of CRC. In addition, it has also been suggested that miR-151a-5p may serve as a useful biomarker for the early detection and treatment of different types of cancer and particularly CRC. However, the specific effects and underlying mechanisms of miR-151a-5p in CRC remain elusive. The results of the current study demonstrated that miR-151a-5p was upregulated in CRC cell lines and clinical tissues derived from patients with CRC. Functionally, the results showed that miR-151a-5p significantly promoted CRC cell proliferation, migration and invasion. Additionally, dual luciferase reporter assays verified that agmatinase (AGMAT) was a direct target of miR-151a-5p and it was positively associated with miR-151a-5p expression. Mechanistically, miR-151a-5p could enhance the epithelial-mesenchymal transition of CRC cells. Taken together, the results of the current study revealed a novel molecular mechanism indicating that the miR-151a-5p/AGMAT axis could serve a crucial role in the regulation of CRC and could therefore be considered as a potential therapeutic strategy for CRC.

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“…The ddPCR allows an absolute quantification of individual nucleotide molecules leading to an excellent quality and comparability of data. We could already confirm the validity of this method in an earlier publication on quantification of nucleic acids under septic conditions [45]. Accordingly, we considered it particularly appropriate for the objectives of this study.…”

Section: Discussionmentioning

confidence: 71%

“…miRNA expression was analyzed by next generation sequencing (NGS) in the Core Unit DNA, Medical Faculty, Leipzig University by means of an Illumina HiScan sequencer (Illumina Inc., San Diego, CA, USA) as previously described [45]. Samples were processed using the TruSeq Small RNA Prep kit v2 (Illumina Inc., San Diego, CA, USA) following the manufacturer's standard protocol.…”

Section: Deep Sequencing and Analysis Of Deep Sequencing Datamentioning

confidence: 99%

Sepsis Diagnostics: Intensive Care Scoring Systems Superior to MicroRNA Biomarker Testing

et al. 2020

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Sepsis represents a serious medical problem accounting for numerous deaths of critically ill patients in intensive care units (ICUs). An early, sensitive, and specific diagnosis is considered a key element for improving the outcome of sepsis patients. In addition to classical laboratory markers, ICU scoring systems and serum miRNAs are discussed as potential sepsis biomarkers. In the present prospective observational study, the suitability of miRNAs in sepsis diagnosis was tested based on proper validated and normalized data (i.e., absolute quantification by means of Droplet Digital PCR (ddPCR)) in direct comparison to classical sepsis markers and ICU scores within the same patient cohort. Therefore, blood samples of septic intensive care patients (n = 12) taken at day of admission at ICU were compared to non-septic intensive care patients (n = 12) and a healthy control group (n = 12). Our analysis indicates that all tested biomarkers have only a moderate informative power and do not allow an unequivocal differentiation between septic and non-septic ICU patients. In conclusion, there is no standalone laboratory parameter that enables a reliable diagnosis of sepsis. miRNAs are not superior to classical parameters in this respect. It seems recommendable to measure multiple parameters and scores and to interpret them with regard to the clinical presentation.

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Identification of stably expressed housekeeping miRNAs in endothelial cells and macrophages in an inflammatory setting

Cited by 14 publications

References 42 publications

Endothelial exosome plays functional role during rickettsial infection

Endothelial exosome plays functional role during rickettsial infection

miR‑151a‑5p promotes the proliferation and metastasis of colorectal carcinoma cells by targeting AGMAT

Sepsis Diagnostics: Intensive Care Scoring Systems Superior to MicroRNA Biomarker Testing

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