Foxo1-mediated inflammatory response after cerebral hemorrhage in rats

Li, Zhenyu; He, Qi; Zhai, Xuan; Yan, You; Li, Lingyu; Hou, Yanghao; He, Fangping; Zhao, Yong; Zhao, Jing

doi:10.1016/j.neulet.2016.06.013

Cited by 42 publications

(27 citation statements)

References 23 publications

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“…LncRNA CRNDE has been reported to correlate with immune process and cytokine response, which elevates the expressions of cytokines, including IL-6, CCL20, CXCL9, and TNFSF18 [36]. Furthermore, it has been proved that FoxO1 knockdown decreases expressions of inflammatory factors, including TNF-α, IL-1β and IL-18 [37], which is consistent with our findings.…”

Section: Discussionsupporting

confidence: 90%

Effects of Long Non-Coding RNA LINC00963 on Renal Interstitial Fibrosis and Oxidative Stress of Rats with Chronic Renal Failure via the Foxo Signaling Pathway

Chen

Zhang

Zhou

et al. 2018

Cell Physiol Biochem

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Background/Aims: Chronic renal failure (CRF) is usually associated with chronic diseases such as congestive heart failure and diabetes mellitus, the prevalence of which is increased with age. This study is designed to investigate the role of long intergenic non-coding RNA (lincRNA) LINC00963 in renal interstitial fibrosis (RIF) and oxidative stress (OS) of CRF via the forkhead box O (FoxO) signaling pathway. Methods: Microarray data and annotated probe files related to CRF were downloaded by retrieving Gene Expression Omnibus (GEO) database to screen differentially expressed lncRNA. Multi Experiment Matrix (MEM) website and dual-luciferase reporter gene assay were used to predict and verify the target gene of LINC00963, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis to identify the major signaling pathways involved. A total of 60 Wistar male rats were randomly selected and divided into the sham (n = 10) and model (n = 50) groups. Five rats in the sham group and thirty rats in the model group were sub-categorized into the control, blank, negative control (NC), LINC00963 vector, si-LINC00963, si-FoxO3, and si-LINC00963 + si-FoxO3 groups (n = 5). Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot analysis were performed to evaluate the expressions of LINC00963, FoxO3a, TGF-β1, FN, GSH-PX, Bax, and Bcl-2. Measurement of changes in OS indexes including BUN, MDA, GSH-Px, SOD, and Na⁺-K⁺-ATP were conducted. Enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of inflammatory factors including TNF-α, IL-6, ICAM-1 and FN. TUNEL staining was performed to evaluate cell apoptosis. Results: LINC00963 was highly expressed in CRF rats and FoxO3 was predicted and then verified as a target gene of LINC00963. FoxO3 gene participated in the FOXO signaling pathway. Compared with the blank and NC groups, there were significantly decreased expressions of LINC00963, TGF-β1, FN, and Bax in the si-LINC00963 group, while increased expressions of GSH-PX, FoxO3a, and Bcl-2. The vitality values of BUN and MDA in the si-LINC00963 group declined, while enzymatic activities of GSH-Px, SOD and Na⁺-K⁺-ATP elevated in comparison to the blank and NC groups. The levels of TNF-α, IL-6, ICAM-1 and FN, and cell apoptosis rate in the si-LINC00963 group decreased in comparison to the blank and NC groups. All the results in the si-LINC00963 group were opposite in the LINC00963 vector and si-FoxO3 groups. Conclusion: Taken together, we conclude that down-regulation of LINC00963 suppresses RIF and OS of CRF by activating the FoxO signaling pathway.

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Section: Discussionsupporting

confidence: 90%

Effects of Long Non-Coding RNA LINC00963 on Renal Interstitial Fibrosis and Oxidative Stress of Rats with Chronic Renal Failure via the Foxo Signaling Pathway

Chen

Zhang

Zhou

et al. 2018

Cell Physiol Biochem

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“… 38 , 39 Here, we used collagenase to induce ICH model and found that the rats showed a setback in the behavioral performance and an increase of BBB permeability as well as brain water content 24 hours after ICH, consistent with the results by others. 22 , 23 , 32 However, pretreating the ICH rats with TF got an improvement of behavioral ability with a decrease of BBB permeability and brain water content ( Figure 1A–D ). It has been known that the leukocytes immediately invading into brain after blooding contributed to disruption of BBB followed by brain edema formation.…”

Section: Discussionmentioning

confidence: 98%

“…Numerous studies have shown that inflammatory response plays an important role in ICH-induced brain injury. 4 , 37 Li et al 32 found that the expression levels of inflammatory cytokines including TNF-α, IL-1β, and IL-18, regulated by Foxo1/TLR4/NF-κβ signaling pathway, were significantly increased at 12 hours post ICH compared with the sham operation group, which was also demonstrated by Yuan et al 16 TNF-α and IL-1β, as the classic pro-inflammatory cytokines, have been proposed to exacerbate ICH-induced brain injury and could induce each other mutually and activate a positive feedback of cellular activation. 7 , 41 IFN-γ, released mainly by activated T lymphocytes and natural killer cells, also has an upregulated expression in the ICH mice 42 and could interact with microglia producing a number of inflammatory cytokines (such as TNF and IL-1) after cerebral ischemia reperfusion, which further aggravated the inflammation.…”

Section: Discussionmentioning

confidence: 99%

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Theaflavin alleviates inflammatory response and brain injury induced by cerebral hemorrhage via inhibiting the nuclear transcription factor kappa β-related pathway in rats

Fu¹,

Wang²,

Cai³

et al. 2018

DDDT

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ObjectiveIntracerebral hemorrhage (ICH) is one of the most common acute cerebrovascular diseases with high mortality. Numerous studies have shown that inflammatory response played an important role in ICH-induced brain injury. Theaflavin (TF) extracted from black tea has various biological functions including anti-inflammatory activity. In this study, we investigated whether TF could inhibit ICH-induced inflammatory response in rats and explored its mechanism.Materials and methodsICH rat models were induced with type VII collagenase and pretreated with TF by gavage in different doses (25 mg/kg–100 mg/kg). Twenty-four hours after ICH attack, we evaluated the rats’ behavioral performance, the blood–brain barrier (BBB) integrity, and the formation of cerebral edema. The levels of reactive oxygen species (ROS) and inflammatory cytokines were examined by 2′,7′-dichlorofluorescin diacetate and enzyme-linked immunosorbent assay. Nissl staining and transferase dUTP nick end labeling (TUNEL) were aimed to detect the neuron loss and apoptosis, the mechanism of which was explored by Western blot.ResultsIt was found that in the pretreated ICH rats TF significantly alleviated the behavioral defects, protected BBB integrity, and decreased the formation of cerebral edema and the levels of ROS as well as inflammatory cytokines (including interleukin-1 beta [IL-1β], IL-18, tumor nectosis factor-alpha, interferon-γ, transforming growth factor beta, and (C-X-C motif) ligand 1 [CXCL1]). Nissl staining and TUNEL displayed TF could protect against the neuron loss and apoptosis via inhibiting the activation of nuclear transcription factor kappa-β-p65 (NF-κβ-p65), caspase-1, and IL-1β. We also found that phorbol 12-myristate 13-acetate, a nonspecific activator of NF-κβ-p65, weakened the positive effect of TF on ICH-induced neural defects and neuron apoptosis by upregulating NF-κβ-related signaling pathway.ConclusionTF could alleviate ICH-induced inflammatory responses and brain injury in rats via inhibiting NF-κβ-related pathway, which may provide a new way for the therapy of ICH.

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“…Activated FOXO1 can upregulate TLR4 expression, thereby activating the MDS innate immune system. The results were consistent with previous studies, FOXO1 is a key regulator of many in ammatory factors, such as TRL4, NF-κB, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-18, via the TLR4/NF-κB signaling pathway [42,43]. In the specimens of MDS patients, we further veri ed that with the increased expression of FOXO1, there is a wide range of upregulation and activation of type I immune cell transcription factors and up-regulation of cellular immune functions, thereby enhancing anti-leukemia effects and inhibiting the growth of MDS malignant clones.…”

Section: Forkhead Box O (Foxo) Transcription Factors Including Foxo1supporting

confidence: 93%

Decitabine induces change of biological traits in myelodysplastic syndromes via FOXO1 activation

Zhang

Yan

et al. 2020

Preprint

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Background: Little is known about the function of tumor suppressor gene Forkhead box 1 (FOXO1) in myelodysplastic syndromes (MDS). The aim of this study was to elucidate the role of FOXO1 through decitabine (DAC) treatment. Methods: Microarray analysis was used to identify differentially expressed genes (DEGs) from 2 MDS cell lines by DAC treatment. WebGestalt was used to perform gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and STRING (Search Tool for the Retrieval of Interacting Genes/Proteins) for constructing protein–protein interaction (PPI) network analysis. Cell apoptosis, cycle arrest, differentiation, and immunoregulation were performed to validate the function of FOXO1 by silencing its expression prior to DAC treatment in MDS. Results: The results showed that the FOXO signaling pathway was one of the most promising. FOXO1 exists in a hyperphosphorylated, inactive form in MDS-L cells. DAC treatment both induces FOXO1 expression and reactivates the protein through reducing its phosphorylation level. Furthermore, we showed that this FOXO1 activation is responsible for the DAC-induced apoptosis, cell cycle arrest, antigen differentiation, and immunoregulation in MDS-L cells. The results also demonstrated that DAC-induced FOXO1 activation upregulated anti-tumor immune response in higher risk MDS specimens.Conclusions: These results suggest that DAC induces FOXO1 activation, which plays an important role in anti-MDS tumors.

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Foxo1-mediated inflammatory response after cerebral hemorrhage in rats

Cited by 42 publications

References 23 publications

Effects of Long Non-Coding RNA LINC00963 on Renal Interstitial Fibrosis and Oxidative Stress of Rats with Chronic Renal Failure via the Foxo Signaling Pathway

Effects of Long Non-Coding RNA LINC00963 on Renal Interstitial Fibrosis and Oxidative Stress of Rats with Chronic Renal Failure via the Foxo Signaling Pathway

Theaflavin alleviates inflammatory response and brain injury induced by cerebral hemorrhage via inhibiting the nuclear transcription factor kappa β-related pathway in rats

Decitabine induces change of biological traits in myelodysplastic syndromes via FOXO1 activation

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Foxo1-mediated inflammatory response after cerebral hemorrhage in rats

Cited by 42 publications

References 23 publications

Effects of Long Non-Coding RNA LINC00963 on Renal Interstitial Fibrosis and Oxidative Stress of Rats with Chronic Renal Failure via the Foxo Signaling Pathway

Effects of Long Non-Coding RNA LINC00963 on Renal Interstitial Fibrosis and Oxidative Stress of Rats with Chronic Renal Failure via the Foxo Signaling Pathway

Theaflavin alleviates inflammatory response and brain injury induced by cerebral hemorrhage via inhibiting the nuclear transcription factor kappa &beta;-related pathway in rats

Decitabine induces change of biological traits in myelodysplastic syndromes via FOXO1 activation

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Theaflavin alleviates inflammatory response and brain injury induced by cerebral hemorrhage via inhibiting the nuclear transcription factor kappa β-related pathway in rats