Dysregulation in microRNA expression in peripheral blood mononuclear cells of sepsis patients is associated with immunopathology

Zhou, Juhua; Chaudhry, Harman; Yin, Zhimin; Ali, Mir Mustafa; Perkins, Linda A.; Owens, William B.; Morales, Juan; McGuire, Franklin R.; Zumbrun, Elizabeth E.; Zhang, Jiajia; Nagarkatti, Prakash

doi:10.1016/j.cyto.2014.09.003

Cited by 85 publications

(51 citation statements)

References 53 publications

(52 reference statements)

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“…Finally, we examined the effect of increasing miR-145 expression in ASM cells from COPD patients upon IL-6 and CXCL8 release. Although studies have suggested a correlation between miR-145 expression and IL-6 & CXCL8 release [55][56][57][58], we show for the first time that increasing the expression of miR-145 can reduce the levels of IL-6 & CXCL8 release from the COPD ASM cells to levels comparable to that of the nonsmoker ASM cells. miR-145 is proposed to target SMAD3 in systemic sclerosis (SSc) [59], cystic fibrosis [23], cartilage dysfunction [60], nasopharyngeal cancer [61] and in hypertrophic scar fibroblasts (HSFBs) [62], we show here that this may also be the case in ASM cells from patients with COPD.…”

contrasting

confidence: 52%

Airway smooth muscle inflammation is regulated by microRNA‐145 in COPD

et al. 2016

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Chronic obstructive pulmonary disease (COPD) is a common, highly debilitating disease of the airways, primarily caused by smoking. Chronic inflammation and structural remodelling are key pathological features of this disease, in part caused by the aberrant function of airway smooth muscle (ASM) cells under the regulation of transforming growth factor (TGF)‐β. miRNA are short, noncoding gene transcripts involved in the negative regulation of specific target genes, through their interactions with mRNA. Previous studies have proposed that mRNA‐145 (miR‐145) may interact with SMAD3, an important downstream signalling molecule of the TGF‐β pathway. TGF‐β was used to stimulate primary human ASM cells isolated from healthy nonsmokers, healthy smokers and COPD patients. This resulted in a TGF‐β‐dependent increase in CXCL8 and IL‐6 release, most notably in the cells from COPD patients. TGF‐β stimulation increased SMAD3 expression, only in cells from COPD patients, with a concurrent increased miR‐145 expression. Regulation of miR‐145 was found to be negatively controlled by pathways involving the MAP kinases, MEK‐1/2 and p38 MAPK. Subsequent, overexpression of miR‐145 (using synthetic mimics) in ASM cells from patients with COPD suppressed IL‐6 and CXCL8 release, to levels comparable to the nonsmoker controls. Therefore, this study suggests that miR‐145 negatively regulates pro‐inflammatory cytokine release from ASM cells in COPD by targeting SMAD3.

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confidence: 52%

Airway smooth muscle inflammation is regulated by microRNA‐145 in COPD

et al. 2016

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“…Microarray analyses, next-generation sequencing, and quantitative RT-PCR are important tools in developing biomarkers [15–21, 50, 51, 53, 57, 71, 97, 107, 119–131]. To date, candidate regulatory RNAs are limited to miRNAs.…”

Section: Discussionmentioning

confidence: 99%

The involvement of regulatory non-coding RNAs in sepsis: a systematic review

Chan

Wong

et al. 2016

Crit Care

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BackgroundSepsis coincides with altered gene expression in different tissues. Accumulating evidence has suggested that microRNAs, long non-coding RNAs, and circular RNAs are important molecules involved in the crosstalk with various pathways pertinent to innate immunity, mitochondrial functions, and apoptosis.MethodsWe searched articles indexed in PubMed (MEDLINE), EMBASE and Europe PubMed Central databases using the Medical Subject Heading (MeSH) or Title/Abstract words (“microRNA”, “long non-coding RNA”, “circular RNA”, “sepsis” and/or “septic shock”) from inception to Sep 2016. Studies investigating the role of host-derived microRNA, long non-coding RNA, and circular RNA in the pathogenesis of and as biomarkers or therapeutics in sepsis were included. Data were extracted in terms of the role of non-coding RNAs in pathogenesis, and their applicability for use as biomarkers or therapeutics in sepsis. Two independent researchers assessed the quality of studies using a modified guideline from the Systematic Review Center for Laboratory animal Experimentation (SYRCLE), a tool based on the Cochrane Collaboration Risk of Bias tool.ResultsObservational studies revealed dysregulation of non-coding RNAs in septic patients. Experimental studies confirmed their crosstalk with JNK/NF-κB and other cellular pathways pertinent to innate immunity, mitochondrial function, and apoptosis. Of the included studies, the SYRCLE scores ranged from 3 to 7 (average score of 4.55). This suggests a moderate risk of bias. Of the 10 articles investigating non-coding RNAs as biomarkers, none of them included a validation cohort. Selective reporting of sensitivity, specificity, and receiver operating curve was common.ConclusionsAlthough non-coding RNAs appear to be good candidates as biomarkers and therapeutics for sepsis, their differential expression across tissues complicated the process. Further investigation on organ-specific delivery of these regulatory molecules may be useful.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-016-1555-3) contains supplementary material, which is available to authorized users.

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“…While to role of miRNAs has largely been studies in cells, miRNAs can also readily be found in the blood. Furthermore, stress-related disorders such as PTSD and major depression are associated with changes in blood-borne miRNA [47, 48] and intracellular tissue miRNA are changed by stressor exposure [49–52]. Because naked circulating miRNAs are degraded quickly in the bloodstream, most blood-borne miRNA are bound to protective proteins, such as high density lipoprotein and argonaute protein [53, 54], or packaged into protective microvesicles, such as exosomes [26, 27].…”

Section: Regulation Of Stress-induced Sterile Inflammation: Mirna Andmentioning

confidence: 99%

Exosomes, DAMPs and miRNA: Features of Stress Physiology and Immune Homeostasis

Fleshner

Crane

2017

Trends in Immunology

163

131

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Psychological/physical stressors and local tissue damage increase inflammatory proteins in tissues and blood in humans and animals, in the absence of pathogenic disease. Stress-evoked cytokine/chemokine responses or “sterile inflammation”, can facilitate host survival and/or negatively impact health, depending on context. Recent evidence supports the hypothesis that systemic stress-evoked sterile inflammation is initiated by the sympathetic nervous system, resulting in the elevation of exosome-associated immune-stimulatory endogenous danger/damage associated molecular patterns (DAMPs) and a reduction in immune-inhibitory microRNA (miRNA) which are carried in the circulation to tissues throughout the body. We propose that sterile inflammation should be considered an elemental feature of the stress response and that circulating exosomes transporting immune- modulatory signals, may play a role fundamental role in immune homeostasis.

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Dysregulation in microRNA expression in peripheral blood mononuclear cells of sepsis patients is associated with immunopathology

Cited by 85 publications

References 53 publications

Airway smooth muscle inflammation is regulated by microRNA‐145 in COPD

Airway smooth muscle inflammation is regulated by microRNA‐145 in COPD

The involvement of regulatory non-coding RNAs in sepsis: a systematic review

Exosomes, DAMPs and miRNA: Features of Stress Physiology and Immune Homeostasis

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