MiR-126 impairs the intestinal barrier function via inhibiting S1PR2 mediated activation of PI3K/AKT signaling pathway

Chen, Tanzhou; Xue, Haibo; Lin, Ruoyang; Huang, Zhiming

doi:10.1016/j.bbrc.2017.03.043

Cited by 31 publications

(24 citation statements)

References 12 publications

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“… 33 , 34 Expression of miR-126 has been previously shown to be higher in IBD biopsies than controls, and miR-126 overexpression contributes to intestinal mucosal barrier dysfunction in vitro. 35 Lastly, miR-126 has been shown to downregulate expression of Iκβα, an important inhibitor of NF-κB signaling pathway. 36 …”

Section: Discussionmentioning

confidence: 99%

Serum miRNAs Are Pharmacodynamic Biomarkers Associated With Therapeutic Response in Pediatric Inflammatory Bowel Disease

Batra

Heier

Diaz-Calderon

et al. 2020

Inflammatory Bowel Diseases

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Background We sought to identify microRNAs (miRNAs) associated with response to anti-TNF-α or glucocorticoids in children with inflammatory bowel disease (IBD) to generate candidate pharmacodynamic and monitoring biomarkers. Methods Clinical response was assessed by Pediatric Crohn’s Disease Activity Index and Pediatric Ulcerative Colitis Activity Index. Quantitative real-time polymerase chain reaction via Taqman Low-Density Array cards were used to identify miRNAs in a discovery cohort of responders (n = 11) and nonresponders (n = 8). Seven serum miRNAs associated with clinical response to treatment, along with 4 previously identified (miR-146a, miR-146b, miR-320a, miR-486), were selected for further study. Candidates were assessed in a validation cohort of serum samples from IBD patients pre- and post-treatment and from healthy controls. Expression of miRNA was also analyzed in inflamed mucosal biopsies from IBD patients and non-IBD controls. Results Discovery cohort analysis identified 7 miRNAs associated with therapeutic response: 5 that decreased (miR-126, miR-454, miR-26b, miR-26a, let-7c) and 2 that increased (miR-636, miR-193b). In the validation cohort, 7 of 11 candidate miRNAs changed in the same direction with response to anti-TNF-α therapies, glucocorticoids, or both. In mucosal biopsies, 7 out of 11 miRNAs were significantly increased in IBD vs healthy controls. Conclusions Five candidate miRNAs associated with clinical response and mucosal inflammation in pediatric IBD patients were identified (miR-126, let-7c, miR-146a, miR-146b, and miR-320a). These miRNAs may be further developed as pharmacodynamic and response monitoring biomarkers for use in clinical care and trials.

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Section: Discussionmentioning

confidence: 99%

Serum miRNAs Are Pharmacodynamic Biomarkers Associated With Therapeutic Response in Pediatric Inflammatory Bowel Disease

Batra

Heier

Diaz-Calderon

et al. 2020

Inflammatory Bowel Diseases

View full text Add to dashboard Cite

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“…Various studies have reported that GRb1 protects against the IR-induced injury of numerous organs, including the heart and kidneys (37,38). Additionally, activation of the PI3K/Akt pathway attenuates injury and alleviates damage to organs, such as the intestine and lungs (39,40). The effects of GRb1 on IIR injury and the underlying mechanisms have not yet been fully investigated.…”

Section: Discussionmentioning

confidence: 99%

Ginsenoside Rb1 attenuates intestinal ischemia/reperfusion‑induced inflammation and oxidative stress via activation of the PI3K/Akt/Nrf2 signaling pathway

Chen

Wang

et al. 2019

Mol Med Report

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Ginsenoside Rb1 (GRb1), one of the major active saponins isolated from ginseng, has recently been reported to protect various organs against ischemia/reperfusion (IR) injury; however, the mechanisms underlying these protective effects following intestinal IR (IIR) remain unclear. The present study aimed to evaluate the effects of GRb1 on IIR injury and determine the mechanisms involved in these effects. Sprague Dawley rats were subjected to 75 min of superior mesenteric artery occlusion, followed by 3 h of reperfusion. GRb1 (15 mg/kg) was administered intraperitoneally 1 h prior to the induction of IIR, with or without intravenous administration of Wortmannin [WM; a phosphoinositide 3-kinase (PI3K) inhibitor, 0.6 mg/kg]. The degree of intestinal injury and oxidative stress-induced damage was determined by histopathologic evaluation and measurement of the serum activity levels of D-lactate, diamine oxidase and endotoxin, and the levels of malondialdehyde (MDA), superoxide dismutase (SOD) and 8-iso-prostaglandin F 2α (8-iso-PGF 2α ). The protein expression levels of p85, phosphorylated (p)-p85, protein kinase B (Akt), p-Akt and nuclear factor erythroid 2-related factor 2 (Nrf2) were determined via western blotting, and the concentrations of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6 were measured via ELISA. It was revealed that IIR led to severe intestinal injury (as determined by significant increases in intestinal Chiu scores), which was accompanied with disruptions in the integrity of the intestinal mucosal barrier. IIR also increased the expression levels of TNF-α, IL-1β, IL-6, MDA and 8-iso-PGF 2α in the intestine, and decreased those of SOD. GRb1 reduced intestinal histological injury, and suppressed inflammatory responses and oxidative stress. Additionally, the protective effects of GRb1 were eliminated by WM. These findings indicated that GRb1 may ameliorate IIR injury by activating the PI3K/protein kinase B/Nrf2 pathway.

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“…Furthermore, IκB, an inhibitor of NFκB, is a downstream target of miR-126-3p and the transfection of a miR-126-3p mimic decreases the expression of IκB in a dose-dependent manner [48]. MiR-126 also impairs intestinal mucosal barrier function under LPS stimulation by targeting S1PR2 through the PI3k/AKT signaling pathway [49]. Functional experiments are required to further clarify its role in axSpA.…”

Section: Discussionmentioning

confidence: 99%

Deregulation of microRNA expression in monocytes and CD4+ T lymphocytes from patients with axial spondyloarthritis

et al. 2019

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BackgroundMicroRNAs (MiRs) play an important role in the pathogenesis of chronic inflammatory diseases. This study is the first to investigate miR expression profiles in purified CD4+ T lymphocytes and CD14+ monocytes from patients with axial spondyloarthritis (axSpA) using a high-throughput qPCR approach.MethodsA total of 81 axSpA patients fulfilling the 2009 ASAS classification criteria, and 55 controls were recruited from October 2014 to July 2017. CD14+ monocytes and CD4+ T lymphocytes were isolated from peripheral blood mononuclear cells. MiR expression was investigated by qPCR using the Exiqon Human MiRnome panel I analyzing 372 miRNAs. Differentially expressed miRNAs identified in the discovery cohort were validated in the replication cohort.ResultsWe found a major difference in miR expression patterns between T lymphocytes and monocytes regardless of the patient or control status. Comparing disease-specific differentially expressed miRs, 13 miRs were found consistently deregulated in CD14+ cells in both cohorts with miR-361-3p, miR-223-3p, miR-484, and miR-16-5p being the most differentially expressed. In CD4+ T cells, 11 miRs were differentially expressed between patients and controls with miR-16-1-3p, miR-28-5p, miR-199a-5p, and miR-126-3p were the most strongly upregulated miRs among patients. These miRs are involved in disease relevant pathways such as inflammation, intestinal permeability or bone formation. Mir-146a-5p levels correlated inversely with the degree of inflammation in axSpA patients.ConclusionsWe demonstrate a consistent deregulation of miRs in both monocytes and CD4+ T cells from axSpA patients, which could contribute to the pathophysiology of the disease with potential interest from a therapeutic perspective.Electronic supplementary materialThe online version of this article (10.1186/s13075-019-1829-7) contains supplementary material, which is available to authorized users.

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MiR-126 impairs the intestinal barrier function via inhibiting S1PR2 mediated activation of PI3K/AKT signaling pathway

Abstract: MiR-126 down-regulated S1PR2 and then prevented the activation of PI3K/AKT signaling pathway, which ultimately could damage intestinal mucosal barrier function.

Cited by 31 publications

References 12 publications

Serum miRNAs Are Pharmacodynamic Biomarkers Associated With Therapeutic Response in Pediatric Inflammatory Bowel Disease

Serum miRNAs Are Pharmacodynamic Biomarkers Associated With Therapeutic Response in Pediatric Inflammatory Bowel Disease

Ginsenoside Rb1 attenuates intestinal ischemia/reperfusion‑induced inflammation and oxidative stress via activation of the PI3K/Akt/Nrf2 signaling pathway

Deregulation of microRNA expression in monocytes and CD4+ T lymphocytes from patients with axial spondyloarthritis

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