PIDD Mediates Radiation-Induced Microglia Activation

Yang, Nong; Gao, Xi; Qu, Xiaofei; Zhang, Ruiguang; Tong, Fan; Cai, Qian; Dong, Jing; Hu, Yu; Wu, Gang; Dong, Xiaorong

doi:10.1667/rr14374.1

Cited by 14 publications

(13 citation statements)

References 42 publications

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“…The NF-κβ pathway plays a vital role in supporting the initiation and progression of tumor cells and resistance to radiation. 24 A previous study 25 showed that the most common adverse reaction that occurs after craniocerebral radiotherapy (CRT) is radiation–induced brain injury (RIBI), and the release of pro-inflammatory cytokines and the activation of microglia in brain tissue induced by CRT played important roles in RIBI. This study also indicates that silencing PIDD (p53-induced protein with a death domain) expression can inhibit the transcriptional activation of microglia by down-regulating the PIDD-C/NF-κβ pathway.…”

Section: Discussionmentioning

confidence: 99%

The Protective Effects and Mechanism of Doxepin on Radiation–Induced Lung Injury in Rats

Wan

Shi

et al. 2022

Dose-Response

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Radiation-induced lung injuries (RILI) is one of the serious complications of radiotherapy posed by the damage of alveolar cells and inflammation over-reaction. We aimed to investigate the potential protective effects of doxepin on RILI (20 Gy total dose at 3 Gy/min of X-ray irradiation), as well as its underlying mechanism. For animal experiments, such parameters as Immunohistochemistry and hematoxylin and eosin (H&E) staining, WBC (white blood cell), CRP (C-reactive protein), Western blot, and q-PCR were detected. The results indicated that both survival status and weight increase of irradiated rats treated by doxepin (3 mg/kg/day, rat) were higher than those of treated with irradiation alone (Dosing started the day before irradiation). Further, histological examinations showed doxepin could tenuate the radiation injury, as indicated as alveolar inflammatory exudation and there was only mild interstitial inflammation infiltration. Western blotting and q-PCR showed that expression of NF-κβ in X group were higher than that in XMD group. For the first time, we reported doxepin functioned as a radioprotectant candidate, which provide a promising application of doxepin for protecting radiotherapy injuries.

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Section: Discussionmentioning

confidence: 99%

The Protective Effects and Mechanism of Doxepin on Radiation–Induced Lung Injury in Rats

Wan

Shi

et al. 2022

Dose-Response

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“…miR-135b-5p overexpression can significantly alleviate hippocampus neuron damage and oxidative stress [ 55 ], and miR-135b-5p can also be a diagnostic marker for mild craniocerebral injury during exercise [ 56 ]. Moreover, studies have also confirmed that Pidd, a critical switch between NF-κB- and radiation-induced apoptosis, can regulate microglial activation induced by radiation [ 57 ]. In contrast, Pidd silencing can inhibit NF-κB activation and reduce inflammation, as inflammation can activate the microglia [ 58 ].…”

Section: Discussionmentioning

confidence: 99%

The functions of fluoxetine and identification of fluoxetine-mediated circular RNAs and messenger RNAs in cerebral ischemic stroke

Zhang

Deng

et al. 2021

Bioengineered

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Fluoxetine is used to improve cognition, exercise ability, depression, and neurological functions in patients with cerebral ischemic stroke. Circular RNAs (circRNAs) play important regulatory roles in multiple diseases. However, studies regarding the fluoxetine-mediated circRNA–microRNA–messenger RNA (mRNA) axis have not been conducted. This study is aim to investigate the functions of fluoxetine and identification of fluoxetine-mediated circRNAs and mRNAs in cerebral ischemic stroke. The middle cerebral artery occlusion (MCAO) rat models were successfully established at fisrt, and then rats were intraperitoneally injected with 10-mg/kg fluoxetine hydrochloride for 14 d. Afterward, the cerebral infarction area was evaluated using triphenyltetrazolium chloride staining. High-throughput sequencing was adopted to screen the differential circRNAs and mRNAs. The candidate circRNAs, mRNAs, and potential microRNAs were verified using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). In addtion, microRNA and circRNA binding was verified using the dual-luciferase reporter assay. Results revealed that fluoxetine markedly diminished the cerebral infarction area in rats after MCAO. The circRNAs and mRNAs were differentially expressed, which includes 879 circRNAs and 815 mRNAs between sham and MCAO groups, respectively, and 958 circRNAs and 838 mRNAs between MCAO and fluoxetine groups, respectively. In which, circMap2k1 and Pidd1 expression was significantly increased in the MCAO group but suppressed after fluoxetine treatment. Moreover, circMap2k1 directly binds with miR-135b-5p. Taken together, we verified that fluoxetine could improve brain injury after cerebral ischemic stroke. Moreover, the circMap2k1/miR-135b-5p/Pidd1 axis is potentially involved in cerebral ischemic stroke.

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“…Cranial irradiation reduced CD206 expression and increased IL1-beta expression in the mouse brain associated with the absence of monocyte-derived macrophages and long-lasting inflammation ( 52 ). Irradiation-induced release of pro-inflammatory cytokines in brain tissue microglial activation might be caused by microglial activation and is mediated by the PIDD-C/NF-κβ transcription pathway ( 53 ). In common, these data reveal immune component of brain TME as potential theraupeutic targets for combined immunotherapy and radiotherapy to treat GBM patients.…”

Section: Discussionmentioning

confidence: 99%

Radiation Effects on Brain Extracellular Matrix

Grigorieva

2020

Front. Oncol.

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Radiotherapy is an important therapeutic approach to treating malignant tumors of different localization, including brain cancer. Glioblastoma multiforme (GBM) represents the most aggressive brain tumor, which develops relapsed disease during the 1st year after the surgical removal of the primary node, in spite of active adjuvant radiochemotherapy. More and more evidence suggests that the treatment's success might be determined by the balance of expected antitumor effects of the treatment and its non-targeted side effects on the surrounding brain tissue. Radiation-induced damage of the GBM microenvironment might create tumor-susceptible niche facilitating proliferation and invasion of the residual glioma cells and the disease relapse. Understanding of molecular mechanisms of radiation-induced changes in brain ECM might help to reconsider and improve conventional anti-glioblastoma radiotherapy, taking into account the balance between its antitumor and ECM-destructing activities. Although little is currently known about the radiation-induced changes in brain ECM, this review summarizes current knowledge about irradiation effects onto the main components of brain ECM such as proteoglycans, glycosaminoglycans, glycoproteins, and the enzymes responsible for their modification and degradation.

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PIDD Mediates Radiation-Induced Microglia Activation

Cited by 14 publications

References 42 publications

The Protective Effects and Mechanism of Doxepin on Radiation–Induced Lung Injury in Rats

The Protective Effects and Mechanism of Doxepin on Radiation–Induced Lung Injury in Rats

The functions of fluoxetine and identification of fluoxetine-mediated circular RNAs and messenger RNAs in cerebral ischemic stroke

Radiation Effects on Brain Extracellular Matrix

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