Increased plasma VEGF levels following ischemic preconditioning are associated with downregulation of miRNA-762 and miR-3072-5p

Ueno, Koji; Samura, Makoto; Nakamura, Tamami; Tanaka, Yuya; Takeuchi, Yuriko; Kawamura, Daichi; Takahashi, Masaya; Hosoyama, Tohru; Morikage, Noriyasu; Hamano, Kimikazu

doi:10.1038/srep36758

Cited by 36 publications

(24 citation statements)

References 46 publications

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“…This further validated the roles of ischemia in promoting DR progression, whereas ischemic postconditioning downregulated retinal VEGF expression in tree shrews that received both STZ administration and cerebral ischemia challenge, indicating the protective roles of PC. Contrary to our experiment results in tree shrews, some studies demonstrated that ischemia or hypoxia conditioning was able to increase VEGF expression [25,26]. Probably, this discrepancy was due to the disease models with different species of animals and different experimental strategies for ischemia or hypoxia conditioning.…”

Section: Discussioncontrasting

confidence: 99%

Ischemic Postconditioning Mitigates Retinopathy in Tree Shrews with Diabetic Cerebral Ischemia

Zhao

Liao

Zhang

et al. 2020

Journal of Diabetes Research

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Ischemic postconditioning (PC) is proved to efficiently protect diabetic patients with acute myocardial infarction from ischemia-reperfusion injury. We aimed to explore the protective roles of ischemic PC on diabetic retinopathy in tree shrews with diabetic cerebral ischemia. A diabetic tree shrew model was established through high-fat diet feeding combined with streptozotocin (STZ) injection, while cortical thrombotic cerebral ischemia was induced photochemically. Tree shrews were divided into the normal control group, sham operation group, diabetes mellitus group, diabetes mellitus+cerebral ischemia group, and diabetes mellitus+cerebral ischemia+PC group (in which the tree shrews with diabetic cerebral ischemia were treated with ischemic PC). H&E staining was used to examine the pathological changes in the retina, and immunohistochemistry was performed to determine the retinal expression of VEGF (vascular endothelial growth factor). The modeling resulted in 77% tree shrews with diabetes. Ischemic PC reduced the blood glucose levels in the tree shrews with diabetic cerebral ischemia. Tree shrews with diabetes had thinned retina with disordered structures, and these pathological changes were aggravated after cerebral ischemia. The retinopathy was alleviated after ischemic PC. Retina expression of VEGF was mainly distributed in the ganglion cell layer in tree shrews. Diabetes and cerebral ischemia increased retinal VEGF expression in a step-wise manner, while additional ischemic PC reduced retinal VEGF expression. Therefore, ischemic PC effectively alleviates retinopathy in tree shrews with diabetic cerebral ischemia, and this effect is associated with reduced retinal VEGF expression.

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Section: Discussioncontrasting

confidence: 99%

Ischemic Postconditioning Mitigates Retinopathy in Tree Shrews with Diabetic Cerebral Ischemia

Zhao

Liao

Zhang

et al. 2020

Journal of Diabetes Research

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“…An important finding is that miR-762 expression was elevated in the EP group at 6 hours as measured by miRNA microarray analysis and validated by qPCR. MiR-762 was identified in remote ischemic preconditioning (rIPC) in mouse CD34 + bone marrow cells supporting its role along with miR-3072-5p in preconditioning [26]. However, to our best knowledge this is the first experiment demonstrating a possible role of miR-762 in the LPS-induced early preconditioning in the mouse kidney.…”

Section: Mirna Microarray Validationmentioning

confidence: 74%

Time-Dependent miRNA Profile in the Mouse Kidney during LPS Preconditioning

P¹,

Róka²,

Kaucsár³

et al. 2020

Preprint

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Background: Pre-treatment with lipopolysaccharide (LPS) protected the kidney against a later lethal ischemia. To reveal the mechanisms of renal cross-tolerance and septic acute kidney injury we investigated the effects of LPS on miRNA expression in the kidney. Methods: Male NMRI mice were injected with 40 and 10 mg/kg LPS ip. and sacrificed at 1.5 and 6 hours (early preconditioning, EP) and at 24 and 48 hours (late preconditioning, LP). The miRNA profile was established using miRCURY LNA™ microarray and confirmed with qPCR. Results: Plasma urea concentration peaked at 24 hours after LPS and decreased thereafter. Renal TNF-α and IL-6 mRNA were extremely elevated at all time-points. miRNome changes were mild at 1.5 hours, most miRNAs were altered at 6 and 24 hours and declined by 48 hours. Not all miRNAs could be assayed or validated by qPCR. In EP miR-762 was newly identified and validated and was the most elevated miRNA with both methods. In LP miR-21a-5p was the most influenced miRNA followed by miR-451a, miR-144-3p and miR-146a-5p. MiR-21a-3p increased significantly in both EP and LP. Conclusion: miR-762 might attenuate the LPS-induced immune response during EP and the miR-144/451 cluster is involved in LPS-induced renal preconditioning.

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“…On the other hand, miR-5126 and miR-6538 has been demonstrated responsive to blood-stage malaria infection, while miR-5126 was confirmed down-regulated in macrophage infected with bacteria Brucella [28]. Of note, they were both down-regulated in exosome extracted from plasma after I/R preconditioning in the abdominal aorta [29], which resembles a mild version of I/R injury in the abdominal circulation. These findings support our result that miR-5126 and miR-6538 decreased in response to intestinal I/R injury and may also be associated with the I/R-induced bacterial translocation in the circulation.…”

Section: Discussionmentioning

confidence: 92%

MicroRNA files in the prevention of intestinal ischemia/reperfusion injury by hydrogen rich saline

et al. 2020

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Background: Hydrogen-rich saline (HRS) has been proven effective against ischemia/reperfusion (I/R) injury. However, knowledge on the underlying signaling events remain poor. Having recent highlight of microRNAs (miRNAs) in mediating intestinal I/R injury, we hypothesized that HRS may protect intestine against I/R injury by regulating miRNAs. Method: Mice were given intraperitoneal injection of saline or HRS once daily for five consecutive days before undergoing intestinal I/R that was induced by 60-min ischemia followed by 180-min reperfusion of superior mesenteric artery. The intestine was collected for histopathological assay, miRNA microarray profiling, Real-Time PCR, and Western blotting. Next, miR-199a-3p mimics or inhibitors were transfected into IEC-6 cells to explore the relationship between HRS treatment and miR-199a-3p. Results: I/R-induced mucosal injury and epithelial cells apoptosis were attenuated by HRS pretreatment. A total of 64 intestinal I/R-responsive miRNAs were altered significantly by HRS pretreatment, in which we validated four novel miRNAs with top significance by was drastically increased by I/R but reduced by HRS. Computational analysis predicts insulin-like growth factor (IGF)-1, mammalian target of rapamycin (mTOR), and phosphoinositide-3-kinase (PI3K) regulatory subunit 1 as targets of miR-199a-3p, suggesting involvement of the pro-survival pathway, IGF-1/PI3K/Akt/mTOR. In in vitro experiment, HRS treatment reduced miR-199a-3p level, increase IGF-1, PI3K and mTOR mRNA expression, restore IEC-6 cells viability, and this protective effects were reversed under miR-199a-3p mimics treatment. Conclusion: Collectively, miR-199a-3p may serve a key role in the anti-apoptotic mechanism of HRS that contributes to its protection of the intestine against I/R injury.

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Increased plasma VEGF levels following ischemic preconditioning are associated with downregulation of miRNA-762 and miR-3072-5p

Cited by 36 publications

References 46 publications

Ischemic Postconditioning Mitigates Retinopathy in Tree Shrews with Diabetic Cerebral Ischemia

Ischemic Postconditioning Mitigates Retinopathy in Tree Shrews with Diabetic Cerebral Ischemia

Time-Dependent miRNA Profile in the Mouse Kidney during LPS Preconditioning

MicroRNA files in the prevention of intestinal ischemia/reperfusion injury by hydrogen rich saline

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