miR-27a is up regulated and promotes inflammatory response in sepsis

Wang, Zhongchuan; Ruan, Zhengshang; Mao, Yanfei; Dong, Wenwen; Zhang, Yun‐Qian; Yin, Na; Jiang, Lai

doi:10.1016/j.cellimm.2014.06.006

Cited by 62 publications

(53 citation statements)

References 20 publications

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“…More excitingly, the levels of many plasma/serum miRNAs and whole blood miRNAs are remarkably changed in endotoxic animals and in patients with sepsis (22, 37, 38). These blood miRNAs might be used as novel diagnostic biomarkers for sepsis (17, 23, 39). In addition, the aberrant expression of miRNAs is also identified in some organs such as lung, liver and heart from endotoxic animals (39-41).…”

Section: Discussionmentioning

confidence: 99%

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Role of MiR-126a-3p in Endothelial Injury in Endotoxic Mice

Chu

Qin

et al. 2016

Critical Care Medicine

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Objective Sepsis poses a serious global health problem with an overall mortality rate of 30%, in which the vascular Injury is a major contributor of. The study is to determine the expression profile of microRNAs in endotoxic vascular walls and their potential roles in sepsis-related vascular injury. Design Prospective randomized study Setting Laboratory investigation Subjects Male C57BL/6 mice, average weight 26.5 ±1.8g. Interventions Endotoxemia was induced in mice via lipopolysaccharide (LPS) injection (20 mg/kg, ip) (Sigma) (25-27). The control mice were injected with the same amount of saline (500 μl, ip). In a sub-group of mice, a high dose of LPS (30mg/kg, ip) was applied to induce endotoxin-related death. Measurements and Main Results The miRNA expression profiles in aortas from lipopolysaccharide (LPS)-induced endotoxic mice were determined. The result demonstrated that some microRNAs were aberrantly expressed in endotoxic mouse arteries. Among them, the endothelial cell enriched/specific miR-126a-3p a-3p was significantly down-regulated in endotoxic mouse arteries, septic human vessels, as well as vascular endothelial cells isolated from endotoxic mice or treated with LPS. The down-regulation of miR-126a-3p occurred at transcriptional level via the decreased expression of krüppel-like factor 2 (KLF2), which could be inhibited by KLF2 over-expression via Ad-KLF2. The down-regulation of miR-126a-3p in endothelial cells resulted in the increased apoptosis, and decreased proliferation and migration, which were inhibited by miR-126a-3p mimics. In vivo, over-expression of miR-126a-3p via lentivirus (LV-miR-126a-3p) attenuated endotoxemia-induced injuries on endothelial function and vascular permeability. We found that SPRED1 and VCAM-1 were two direct target genes of miR-126a-3p related to miR-126a-3p-mediated effects in endotoxemia. Finally, the survival rate of endotoxic mice was significantly increased by the over-expression of miR-126a-3p. Conclusions The results suggest that vascular microRNAs such as miR-126a-3p may represent novel mechanisms and new therapeutic targets for endotoxemia-induced vascular injury and endotoxic mortality.

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Section: Discussionmentioning

confidence: 99%

“…These blood miRNAs might be used as novel diagnostic biomarkers for sepsis (17, 23, 39). In addition, the aberrant expression of miRNAs is also identified in some organs such as lung, liver and heart from endotoxic animals (39-41). These discoveries indicate that miRNAs might play important roles in sepsis.…”

Section: Discussionmentioning

confidence: 99%

Role of MiR-126a-3p in Endothelial Injury in Endotoxic Mice

Chu

Qin

et al. 2016

Critical Care Medicine

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“…Based on this, the authors examined the neutralization of miR-27a in a murine cecal ligation and puncture sepsis model. 92 In those septic mice, inhibition of miR-27a was accompanied by reduced expression levels of proinflammatory cytokines such as tumor necrosis factor-α and IL-6 and diminished pulmonary inflammation and revealed a benefit in survival of septic mice. This is also in accordance with a study that identified IL-10, a major antiinflammatory cytokine, as direct miR-27a target in human peripheral blood mononuclear cells.…”

Section: Mirna Functions In Perioperative Medicinementioning

confidence: 93%

“…75,76,89–91 Very recent findings from a functional study in a murine sepsis model revealed expressional changes of diverse miRNAs including the proinflammatory miR-27a during sepsis induction. 92 Previous studies revealed that the antiinflammatory gene peroxisome proliferator–activated receptor (PPAR) γ is one of the several genes miR-27a can target and reported that it is negatively regulated by miR-27a in adipocyte differentiation. 93 The three different PPARs, α, β/δ, and γ, are differentially expressed and represent nuclear receptor proteins that function as transcription factors.…”

Section: Mirna Functions In Perioperative Medicinementioning

confidence: 99%

“…92,105–107 Analysis of extracellular miRNAs could also help identifying the early onset of acute kidney injury (AKI). Kidney failure presents a frequent perioperative complication, and even minor increases of perioperative creatinine levels are associated with prolonged hospital length of stay and increased mortality.…”

Section: Mirna Functions In Perioperative Medicinementioning

confidence: 99%

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Emerging Roles for MicroRNAs in Perioperative Medicine

et al. 2016

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MicroRNAs (miRNAs) are small, non–protein-coding, single-stranded RNAs. They function as posttranscriptional regulators of gene expression by interacting with target mRNAs. This process prevents translation of target mRNAs into a functional protein. miRNAs are considered to be functionally involved in virtually all physiologic processes, including differentiation and proliferation, metabolism, hemostasis, apoptosis, and inflammation. Many of these functions have important implications for anesthesiology and critical care medicine. Studies indicate that miRNA expression levels can be used to predict the risk for eminent organ injury or sepsis. Pharmacologic approaches targeting miRNAs for the treatment of human diseases are currently being tested in clinical trials. The present review highlights the important biological functions of miRNAs and their usefulness as perioperative biomarkers and discusses the pharmacologic approaches that modulate miRNA functions for disease treatment. In addition, the authors discuss the pharmacologic interactions of miRNAs with currently used anesthetics and their potential to impact anesthetic toxicity and side effects.

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miR‐34b‐3p protects against acute kidney injury in sepsis mice via targeting ubiquitin‐like protein 4A

Wang

Pei

et al. 2020

The Kaohsiung J of Med Scie

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MicroRNAs (miRNAs) have been reported as a diagnostic markers for sepsis, and miRNAs have also been found to play a regulatory role in sepsis-induced acute kidney injury (AKI). However, the regulatory effect and mechanism of miR-34b-3p on AKI remains elusive. First, sepsis mice with AKI was established via cecal ligation puncture (CLP), and verified through hematoxylin-eosin staining, determination of tumor necrosis factor-α (TNF-α), interleukin (IL)-6/1β and serum levels of alanine aminotransferase (ALT) and blood urea nitrogen (BUN). Data showed that CLP-induced mice demonstrated increased ALT, BUN, TNF-α, IL-1β, and IL-6 with injured pathological morphology of kidney tissues. Second, lipopolysaccharide (LPS) treatment elevated TNF-α, IL-1β, and IL-6 contents in rat mesangial cells (RMCs). MiR-34b-3p was downregulated in both CLP-induced mice and LPS-induced RMCs. Third, target gene of miR-34b-3p was verified as ubiquitin-like protein 4A (UBL4A), and UBL4A was upregulated in LPSinduced RMCs. MiR-34b-3p could inhibit UBL4A expression and decreased TNF-α, IL-1β and IL-6 contents in LPS-induced RMCs, while overexpression of UBL4A counteract with the suppressive effects of miR-34b-3p on the protein expression. Moreover, transcriptional activity of UBL4A-induced NF-κB was decreased by miR-34b-3p. Lastly, in vivo injection of miR-34b-3p agomir improved CLP-induced kidney tissues injury with declined ALT, BUN, TNF-α, IL-1β, IL-6, and UBL4A. In general, miR-34b-3p overexpression could alleviate AKI in sepsis mice through downregulation of UBL4A/NF-κB, providing potential therapeutic strategy for AKI.

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miR-27a is up regulated and promotes inflammatory response in sepsis

Cited by 62 publications

References 20 publications

Role of MiR-126a-3p in Endothelial Injury in Endotoxic Mice

Role of MiR-126a-3p in Endothelial Injury in Endotoxic Mice

Emerging Roles for MicroRNAs in Perioperative Medicine

miR‐34b‐3p protects against acute kidney injury in sepsis mice via targeting ubiquitin‐like protein 4A

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