CDKN1B Mediates Apoptosis of Neuronal Cells and Inflammation Induced by Oxyhemoglobin via miR-502-5p After Subarachnoid Hemorrhage

Chen, Dong; Wang, Xianwei; Huang, Jiaming; Cui, Sifu; Zhang, Liqiang

doi:10.1007/s12031-020-01512-z

Cited by 15 publications

(11 citation statements)

References 28 publications

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“…Although this study did not describe the specific downstream effectors which regulate these processes, it suggests that the elevated Pten expression makes neurons more sensitive to ischemia-reperfusion injury, as observed by increased apoptosis markers caspase-3 and -8, which suppressed cell viability over time. More evidence for X-linked miR regulation of neuronal apoptosis comes from the fact that miR-502 expression was increased in cultured neurons (a murine HT22 nerve cell line) under inflammatory conditions which led to a decrease in Cdkn1b expression, also known as p27KIP1, which negatively regulates cellular proliferation via cyclin dependent kinases [ 81 ]. As a result, more apoptosis of this cell line was observed.…”

Section: Stroke Promoting Mechanismsmentioning

confidence: 99%

Sex-Specific MicroRNAs in Neurovascular Units in Ischemic Stroke

Florijn

Bijkerk

Kruyt

et al. 2021

IJMS

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Accumulating evidence pinpoints sex differences in stroke incidence, etiology and outcome. Therefore, more understanding of the sex-specific mechanisms that lead to ischemic stroke and aggravation of secondary damage after stroke is needed. Our current mechanistic understanding of cerebral ischemia states that endothelial quiescence in neurovascular units (NVUs) is a major physiological parameter affecting the cellular response to neuron, astrocyte and vascular smooth muscle cell (VSMC) injury. Although a hallmark of the response to injury in these cells is transcriptional activation, noncoding RNAs such as microRNAs exhibit cell-type and context dependent regulation of gene expression at the post-transcriptional level. This review assesses whether sex-specific microRNA expression (either derived from X-chromosome loci following incomplete X-chromosome inactivation or regulated by estrogen in their biogenesis) in these cells controls NVU quiescence, and as such, could differentiate stroke pathophysiology in women compared to men. Their adverse expression was found to decrease tight junction affinity in endothelial cells and activate VSMC proliferation, while their regulation of paracrine astrocyte signaling was shown to neutralize sex-specific apoptotic pathways in neurons. As such, these microRNAs have cell type-specific functions in astrocytes and vascular cells which act on one another, thereby affecting the cell viability of neurons. Furthermore, these microRNAs display actual and potential clinical implications as diagnostic and prognostic biomarkers in ischemic stroke and in predicting therapeutic response to antiplatelet therapy. In conclusion, this review improves the current mechanistic understanding of the molecular mechanisms leading to ischemic stroke in women and highlights the clinical promise of sex-specific microRNAs as novel diagnostic biomarkers for (silent) ischemic stroke.

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Section: Stroke Promoting Mechanismsmentioning

confidence: 99%

Sex-Specific MicroRNAs in Neurovascular Units in Ischemic Stroke

Florijn

Bijkerk

Kruyt

et al. 2021

IJMS

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“…According to several databases, CDKN1B was considered the potential target gene. Generally, Cyclindependent kinase inhibitor 1B (CDKN1B) encodes p27, which is a well-known tumor-inhibiting factor from the Kinase Inhibitory Protein (Kip) family (51,52). Because of the ability to regulate the cell cycle and growth, CDKN1B is known as a tumor suppressor (53).…”

Section: Discussionmentioning

confidence: 99%

“…It must be noted that there are controversies over CDKN1B's effect on cell apoptosis. Chen et al (51) demonstrated that oxyhemoglobin reduced the level of CDKN1B in neuronal cells, inducing apoptosis and inflammation. CDKN1B overexpression would reverse the negative effect of oxyhemoglobin.…”

Section: Discussionmentioning

confidence: 99%

Exosome-derived miR-196b-5p facilitates intercellular interaction in infantile hemangioma via down-regulating CDKN1B

Wang¹,

Zhao²,

Liu³

et al. 2021

Ann Transl Med

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Background: Though infantile hemangioma (IH) is a common benign vascular tumor, its pathogenesis remains unclear. This study explored the function of hemangioma-derived stem cells (HemSCs) derived exosomes, which exerted an intercellular effect on hemangioma-derived endothelial cells (HemECs).Methods: First, HemSCs and HemECs were extracted and cultured. HemSCs derived exosomes (HemSCsexos) were harvested. miRNA sequencing and target prediction were used to explore differentially expressed miRNAs and potential binding targets. After HemECs were co-cultured with HemSCs-exos, a series of in vitro assays were then performed including cell counting kit-8 (CCK-8) assay, cell apoptosis assay, cell cycle assay and tube formation assay to evaluate proliferation, angiogenesis abilities, etc. qRT-PCR and Western blot were conducted to detect the expression level of target genes and proteins.Results: After co-culturing with HemSCs-exos, proliferation, and angiogenesis abilities of HemECs were enhanced, while apoptosis and cell cycle arrest rate were decreased. MiR-196b-5p was observed to be significantly highly expressed in HemSCs-exos. CDKN1B was identified as the binding target of miR-196b-5p. HemECs' proliferation and angiogenesis abilities were elevated when co-cultured with exosomes from HemSCs transfected with miR-196b-5p mimic. In addition, apoptosis rate declined, and lower cells were arrested in G0/G1 phases. Cyclin E, bcl-2 were significantly highly expressed, whereas p27, Bax expression were significantly down-regulated. The positive effect of miR-196b-5p in HemSCs-exos was dramatically reversed when HemECs were transfected with oe-CDKN1B. Conclusions:The current study found a novel intercellular interaction between IH cells. Briefly, exosomederived miRNA-196b-5p in HemSCs could facilitate proliferation and angiogenesis abilities, and attenuate apoptosis and cell cycle repression rate of HemECs by directly binding with CDKN1B.

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“…Regulation of peroxisome proliferator-activated receptor-gamma (PPAR-γ) signaling pathway plays a crucial role in the protection of neural cell functions after SAH [ 238 ]. Activation of PPAR-γ receptors potently inhibits the expression and activity of TLR4 [ 239 ].…”

Section: The Role Of Toll-like Receptors In Cvdsmentioning

confidence: 99%

Toll-Like Receptor Signaling Pathways: Novel Therapeutic Targets for Cerebrovascular Disorders

Ahmadabad

Mirzaasgari

Gorji

et al. 2021

IJMS

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Toll-like receptors (TLRs), a class of pattern recognition proteins, play an integral role in the modulation of systemic inflammatory responses. Cerebrovascular diseases (CVDs) are a group of pathological conditions that temporarily or permanently affect the brain tissue mostly via the decrease of oxygen and glucose supply. TLRs have a critical role in the activation of inflammatory cascades following hypoxic-ischemic events and subsequently contribute to neuroprotective or detrimental effects of CVD-induced neuroinflammation. The TLR signaling pathway and downstream cascades trigger immune responses via the production and release of various inflammatory mediators. The present review describes the modulatory role of the TLR signaling pathway in the inflammatory responses developed following various CVDs and discusses the potential benefits of the modulation of different TLRs in the improvement of functional outcomes after brain ischemia.

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CDKN1B Mediates Apoptosis of Neuronal Cells and Inflammation Induced by Oxyhemoglobin via miR-502-5p After Subarachnoid Hemorrhage

Cited by 15 publications

References 28 publications

Sex-Specific MicroRNAs in Neurovascular Units in Ischemic Stroke

Sex-Specific MicroRNAs in Neurovascular Units in Ischemic Stroke

Exosome-derived miR-196b-5p facilitates intercellular interaction in infantile hemangioma via down-regulating CDKN1B

Toll-Like Receptor Signaling Pathways: Novel Therapeutic Targets for Cerebrovascular Disorders

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