TGF-β2/Smad3 Signaling Pathway Activation Through Enhancing VEGF and CD34 Ameliorates Cerebral Ischemia/Reperfusion Injury After Isoflurane Post-conditioning in Rats

Li, Peng; Yin, Jiangwen; Wang, Sheng; Ge, Ming; Han, Zhaobin; Wu, Yan; Zhang, Meng; Xie, Liping; Li, Yan

doi:10.1007/s11064-019-02880-8

Cited by 23 publications

(16 citation statements)

References 43 publications

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“…Activation of TGF-β signaling has diverse functions, including an increase in angiogenesis and neurogenesis. 51 , 52 Neuronal apoptosis is another indicator of ischemia injury. Smad3 is closely involved with apoptosis.…”

Section: Discussionmentioning

confidence: 99%

“… 51 A previous study demonstrated that overexpression of Smad3 not only plays an anti-apoptotic role after cerebral ischemia and reperfusion but also has the potential to inhibit inflammation and reduce acute brain injury. 52 Our results indicated that circUCK2 activates the downstream TGF-β/Smad3 signaling pathway via modulating miR-125b-5p/GDF11 expression, thereby improving the cell survival rate and ameliorating OGD-induced neuronal injury.…”

Section: Discussionmentioning

confidence: 99%

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RETRACTED: Overexpression of circRNA circUCK2 Attenuates Cell Apoptosis in Cerebral Ischemia-Reperfusion Injury via miR-125b-5p/GDF11 Signaling

Chen

Wang

Feng

et al. 2020

Molecular Therapy - Nucleic Acids

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Circular RNAs (circRNAs) are expressed at high levels in the brain and are involved in various central nervous system diseases. However, the potential role of circRNAs in ischemic stroke-associated neuronal injury remains largely unknown. Herein, we uncovered the function and underlying mechanism of the circRNA UCK2 (circUCK2) in ischemia stroke. The oxygen-glucose deprivation model in HT-22 cells was used to mimic ischemia stroke in vitro . Neuronal viability and apoptosis were determined by Cell Counting Kit-8 (CCK-8) assays and TUNEL (terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate nick end labeling) staining, respectively. Middle cerebral artery occlusion was conducted to evaluate the function of circUCK2 in mice. The levels of circUCK2 were significantly decreased in brain tissues from a mouse model of focal cerebral ischemia and reperfusion. Upregulated circUCK2 levels significantly decreased infarct volumes, attenuated neuronal injury, and improved neurological deficits. circUCK2 reduced oxygen glucose deprivation (OGD)-induced cell apoptosis by regulating transforming growth factor β (TGF-β)/mothers against decapentaplegic homolog 3 (Smad3) signaling. Furthermore, circUCK2 functioned as an endogenous miR-125b-5p sponge to inhibit miR-125b-5p activity, resulting in an increase in growth differentiation factor 11 (GDF11) expression and a subsequent amelioration of neuronal injury. Consequently, these findings showed that the circUCK2/miR-125b-5p/GDF11 axis is an essential signaling pathway during ischemia stroke. Thus, the circRNA circUCK2 may serve as a potential target for novel treatment in patients with ischemic stroke.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

RETRACTED: Overexpression of circRNA circUCK2 Attenuates Cell Apoptosis in Cerebral Ischemia-Reperfusion Injury via miR-125b-5p/GDF11 Signaling

Chen

Wang

Feng

et al. 2020

Molecular Therapy - Nucleic Acids

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“…The VEGF signalling pathway regulates angiogenesis of various organs and tissues and alleviates adaptive cerebral ischaemia/reperfusion injury in rats [ 33 ]. Exosomal MMP2 from mature osteoblasts promotes endothelial cell angiogenesis through the VEGF signalling pathway [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

Exosomal circRNAs contribute to intestinal development via the VEGF signalling pathway in human term and preterm colostrum

Zhou

Wang

et al. 2021

Aging

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Human breast milk (HBM) provides essential nutrients for newborn growth and development, and contains a variety of biologically active ingredients that can affect gastrointestinal tract and immune system development in breastfed infants. HBM also contains mRNAs, microRNAs and lncRNAs, most of which are encapsulated in milk-derived exosomes and exhibit various important infant development related biological functions. While previous studies have shown that exosomal circRNAs are involved in the intestinal epithelial cells’ proliferation and repair. However, the effect of HBM exosomal circRNAs on intestinal development is not clear. In this study, we identified 6756 circRNAs both in preterm colostrum (PC) and term colostrum (TC), of which 66 were upregulated, and 42 were downregulated (|fold change>2|, p < 0.05) in PC. Pathway analysis showed that the VEGF signalling pathway was involved, and network analysis revealed that the differentially expressed circRNAs bound various miRNAs. Further analyses showed that has_circRNA_405708 and has_circRNA_104707 were involved in the VEGF signalling pathway, and that they all bound various mirRNAs. Exosomes found in preterm colostrum (PC) and term colostrum (TC) promoted VEGF protein expression and induced the proliferation and migration of small intestinal epithelial cells (FHCs). Exosomal circRNAs found in human colostrum (HC) binding to related miRNAs may regulate VEGF signalling, and intestinal development.

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“…These results suggest that ISO treatment is likely to activate the TGF-β2/Smad3 signaling pathway. 23 TGF-β2 has been recognized as a necessary protective molecule of the central nervous system, and experiment has confirmed the protective effect of TGF-β2. 24 The TGF-β2/Smad3 signaling pathway participates in and regulates the expression of VEGF and CD34, promoting the repair of cerebral microvascular network after I/R.…”

Section: E Xisting S Ignaling P Athways and B Rief M mentioning

confidence: 95%

Current research progress of isoflurane in cerebral ischemia/reperfusion injury

Xue

Chen

et al. 2022

Medical Gas Research

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Cerebral ischemia/reperfusion injury is an important factor leading to poor prognosis in ischemic stroke patients. Therefore, it is particularly important to find effective remedial measures to promote the health of patients to return to society. Isoflurane is a safe and reliable anesthetic gas with a long history of clinical application. In recent years, its protection function to human body has been widely recognized, and nowadays isoflurane for cerebral protection has been widely studied, and the stable effect of isoflurane has satisfied many researchers. Basic studies have shown that isoflurane’s protection of brain tissue after ischemia/reperfusion involves a variety of signaling pathways and effector molecules. Even though many signaling pathways have been described, more and more studies focus on exploring their mechanisms of action, in order to provide strong evidence for clinical application. This could prompt the introduction of isoflurane therapy to clinical patients as soon as possible. In this paper, several confirmed signaling pathways will be reviewed to find possible strategies for clinical treatment.

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TGF-β2/Smad3 Signaling Pathway Activation Through Enhancing VEGF and CD34 Ameliorates Cerebral Ischemia/Reperfusion Injury After Isoflurane Post-conditioning in Rats

Cited by 23 publications

References 43 publications

RETRACTED: Overexpression of circRNA circUCK2 Attenuates Cell Apoptosis in Cerebral Ischemia-Reperfusion Injury via miR-125b-5p/GDF11 Signaling

RETRACTED: Overexpression of circRNA circUCK2 Attenuates Cell Apoptosis in Cerebral Ischemia-Reperfusion Injury via miR-125b-5p/GDF11 Signaling

Exosomal circRNAs contribute to intestinal development via the VEGF signalling pathway in human term and preterm colostrum

Current research progress of isoflurane in cerebral ischemia/reperfusion injury

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