Rev-erbα regulates hepatic ischemia-reperfusion injury in mice

Lin, Luomin; Wang, Shuai; Wu, Baojian

doi:10.1016/j.bbrc.2020.06.152

Cited by 11 publications

(6 citation statements)

References 24 publications

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“…Consistently, NLRP3 deficiency protects against liver I/R injury in mice ( 191 ). Accordingly, Rev-erbα deletion sensitizes mice to hI/R and is accompanied by exacerbated NLRP3 activation and pro-inflammatory cytokine secretion ( 168 ). On the contrary, SR9009 treatment alleviates hI/R-induced hepatic damage by inhibiting IL-1β expression ( 168 ).…”

Section: Regulatory Function Of Nr In Nlrp3-driven Diseases and Theirmentioning

confidence: 99%

“…Accordingly, Rev-erbα deletion sensitizes mice to hI/R and is accompanied by exacerbated NLRP3 activation and pro-inflammatory cytokine secretion ( 168 ). On the contrary, SR9009 treatment alleviates hI/R-induced hepatic damage by inhibiting IL-1β expression ( 168 ). In conclusion, Rev-erbs, ROR γ , VDR, PPAR β / δ , and FXR then exhibit hepatoprotective effects in acute liver inflammatory diseases by dampening the NLRP3 inflammasome activity.…”

Section: Regulatory Function Of Nr In Nlrp3-driven Diseases and Theirmentioning

confidence: 99%

“…By contrast, activation of Rev-erbs with heme, their natural ligand, or with synthetic ligands reduces the secretion of these cytokines by inhibiting the expression of NLRP3 inflammasome component genes ( 132 ). Strikingly, the susceptibility to fulminant hepatitis and hepatic ischemia reperfusion injury is time-of-day dependent, upon the control of the molecular clock with Rev-erbα as an important regulator of the inflammasome ( 132 , 168 ). Remarkably, pharmacological activation of both Rev-erbs and ROR reduces liver injury and improves the survival time and rate in a NLRP3-dependent manner in treated mice ( 132 , 133 ).…”

Section: Nr-dependent Control Of Nlrp3 Circadian Rhythmicity and Chromentioning

confidence: 99%

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Nuclear Receptors in the Control of the NLRP3 Inflammasome Pathway

Duez

Pourcet

2021

Front. Endocrinol.

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The innate immune system is the first line of defense specialized in the clearing of invaders whether foreign elements like microbes or self-elements that accumulate abnormally including cellular debris. Inflammasomes are master regulators of the innate immune system, especially in macrophages, and are key sensors involved in maintaining cellular health in response to cytolytic pathogens or stress signals. Inflammasomes are cytoplasmic complexes typically composed of a sensor molecule such as NOD-Like Receptors (NLRs), an adaptor protein including ASC and an effector protein such as caspase 1. Upon stimulation, inflammasome complex components associate to promote the cleavage of the pro-caspase 1 into active caspase-1 and the subsequent activation of pro-inflammatory cytokines including IL-18 and IL-1β. Deficiency or overactivation of such important sensors leads to critical diseases including Alzheimer diseases, chronic inflammatory diseases, cancers, acute liver diseases, and cardiometabolic diseases. Inflammasomes are tightly controlled by a two-step activation regulatory process consisting in a priming step, which activates the transcription of inflammasome components, and an activation step which leads to the inflammasome complex formation and the subsequent cleavage of pro-IL1 cytokines. Apart from the NF-κB pathway, nuclear receptors have recently been proposed as additional regulators of this pathway. This review will discuss the role of nuclear receptors in the control of the NLRP3 inflammasome and the putative beneficial effect of new modulators of inflammasomes in the treatment of inflammatory diseases including colitis, fulminant hepatitis, cardiac ischemia–reperfusion and brain diseases.

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Section: Regulatory Function Of Nr In Nlrp3-driven Diseases and Theirmentioning

confidence: 99%

Section: Regulatory Function Of Nr In Nlrp3-driven Diseases and Theirmentioning

confidence: 99%

Section: Nr-dependent Control Of Nlrp3 Circadian Rhythmicity and Chromentioning

confidence: 99%

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Nuclear Receptors in the Control of the NLRP3 Inflammasome Pathway

Duez

Pourcet

2021

Front. Endocrinol.

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“…It was shown that Rev-erbα activation by SR9009, the synthetic ligand for Rev-erbs, inhibited LPS-stimulated transcription of inflammatory factors IL-1β, IL-6, MMP-9 and Ccl2 in astrocytes (Morioka et al, 2019). SR9009 significantly attenuated hepatic damage and inflammatory responses (Lin et al, 2020a). SR9009 administration in mice at 1 day after myocardial ischemic-reperfusion prevents the heart failure by targeting the cardiac inflammasome (Reitz et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Rev-erbα agonist SR9009 protects against cerebral ischemic injury through mechanisms involving Nrf2 pathway

Sheng

Chen

et al. 2023

Front. Pharmacol.

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Backgrounds: The circadian clock protein Rev-erbα is a crucial regulator of circadian rhythms that affects multiple molecular, cellular, and physiology pathways that control susceptibility, injury, and recovery in the neurological disorders. Emerging evidence suggest that Rev-erbα plays a key role in the inflammation and oxidative stress, two pivotal mechanisms in the pathogenesis, progression, and recovery process of ischemic stroke. However, it remains inconclusive whether Rev-erbα activation is protective against ischemic brain damage. Nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, a master regulator of inflammatory and oxidative responses. Our study aimed to determine whether pharmacological activation of Rev-erbα by SR9009 protects against acute ischemic brain damage partly via Nrf2 pathway.Methods: Adult mice were pretreated with SR9009 or Nrf2 inhibitor all-trans-retinoic acid (ATRA) for 3 days prior to Sham or middle cerebral artery occlusion (MCAO) operation. After ischemia for 1 h and reperfusion for 24 h, the neurological function and cerebral infarction volume were determined, superoxide dismutase (SOD) activity, malondialdehyde (MDA) content and glutathione peroxidase (GSH-PX) activity in serum were detected by kit. The mRNA and/or protein level of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), inducible nitric oxide synthase (iNOS), Period (Per)1, Brain and muscle arnt-like1 (Bmal1), Circadian locomotor output cycles kaput (Clock), Rev-erbα, Nrf2, heme oxygenase-1 (HO-1) and quinone oxidoreductase 1 (NQO1) in cerebral cortex were detected by q-PCR and Western blot.Results: We confirmed that SR9009 activated Rev-erbα gene in the cerebral cortex under basal condition. At 24 h after reperfusion, SR9009 ameliorated acute neurological deficits, reduced infarct volume. Meanwhile, the inflammatory TNF-α, IL-1β, iNOS and MDA content levels were significant decreased, SOD and GSH-PX activity were obviously increased, which were markedly blunted (or abolished) by ATRA. SR9009 enhanced the induction of Nrf2 and its downstream target genes HO-1 and NQO1 after ischemic insult. In addition, we found that SR9009 restored Rev-erbα, Bmal1, Clock, Per1 genes expression in the cerebral cortex under ischemic condition.Conclusion: Taken together, Rev-erbα activation by SR9009 protects against ischemic stroke damage, at least, partly through Nrf2 pathway.

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“…Ischemia/reperfusion (I/R) injury refers to the pathological process that exacerbates tissue and organ injury when blood flow is restored after a prolonged period of ischemia [11,12]. Several tissues and organs of the body are susceptible to I/R injury, including the liver, brain, myocardium, kidney, gastrointestinal tract, and skin [13][14][15][16]. Consequently, how to prevent and treat I/R injury in ischemic tissues or organs has become a current hot topic.…”

Section: Introductionmentioning

confidence: 99%

Sodium Danshensu Cream Promotes the Healing of Pressure Ulcers in Mice through the Nrf2/HO-1 and NF-κB Pathways

Yang

Shen

2022

Pharmaceuticals

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On the basis of the mice pressure ulcers (PU) model, the protective effect and potential mechanism of sodium Danshensu (SDSS) cream against PU were investigated. The mice were randomly divided into three groups: the negative control group (cream without 0.5 g SDSS), the SDSS group (cream containing 0.5 g SDSS), and the positive group (0.5 g Hirudoid®). After 7 and 14 days of ointment application, the wound-healing rate of the SDSS and positive groups was significantly higher than that of the control group (p < 0.05). The results of hematoxylin–eosin staining also indicated that SDSS has the potential to promote the healing of PU. In addition, the serum IL-6, IL-1β, TNF-α, and MDA levels decreased significantly (p < 0.01) after 14 days of SDSS treatment, while the SOD, CAT, and GSH-Px activities increased significantly (p < 0.01). In addition, SDSS cream was able to significantly increase the expression of Nrf2, HO-1, GCLM, NQO1, NF-κB p65, NF-κB p50, IKKα, and IKKβ while decreasing the expression of Keap1 and IκBαin the Nrf2/HO-1 and NF-κB pathways. Our research will provide a foundation for the future clinical prevention and treatment of PU with SDSS cream.

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Rev-erbα regulates hepatic ischemia-reperfusion injury in mice

Cited by 11 publications

References 24 publications

Nuclear Receptors in the Control of the NLRP3 Inflammasome Pathway

Nuclear Receptors in the Control of the NLRP3 Inflammasome Pathway

Rev-erbα agonist SR9009 protects against cerebral ischemic injury through mechanisms involving Nrf2 pathway

Sodium Danshensu Cream Promotes the Healing of Pressure Ulcers in Mice through the Nrf2/HO-1 and NF-κB Pathways

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