Cold-inducible RNA-binding protein mediates neuroinflammation in cerebral ischemia

Zhou, Mian; Yang, Weng Lang; Ji, Youxin; Qiang, Xiaoling; Wang, Haichao

doi:10.1016/j.bbagen.2014.02.027

Cited by 87 publications

(98 citation statements)

References 39 publications

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“…17, 18 We have demonstrated that Cirp −/− mice exhibit less tubular epithelial injury after RIR on histology corresponding to lower levels of serum injury markers BUN and creatinine. This is consistent with previous studies in which Cirp −/− mice show less organ injury after hemorrhage 12 and reduced brain infarct size after ischemic stroke 19 compared to WT mice.…”

Section: Discussionsupporting

confidence: 93%

Deficiency of cold-inducible ribonucleic acid-binding protein reduces renal injury after ischemia-reperfusion

Cen

Yang

Yen

et al. 2016

Surgery

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Background Renal ischemia-reperfusion (RIR) injury, commonly caused by major surgery and shock, leads to acute kidney injury, and is associated with high morbidity and mortality. Cold-inducible RNA-binding protein (CIRP), a cold shock protein, has been recently identified as a damage-associated molecular pattern (DAMP). We hypothesized that CIRP exacerbates severity of injury in RIR. Methods Renal ischemia was induced in 8-week-old male C57BL/6 wild-type (WT) mice and Cirp−/− mice via bilateral clamping of renal pedicles for 30 min, followed by reperfusion for 5 h or 24 h and harvest of blood and renal tissue for analysis. Anti-CIRP antibody or non-immunized IgG was injected intravenously (10 mg/kg body weight) at time of reperfusion. Results After RIR, Cirp−/− mice demonstrated a reduction of BUN and creatinine of 53% and 60%, respectively, compared to WT mice. Serum IL-6 levels were significantly reduced 70% in Cirp−/− mice compared to WT mice after RIR. Levels of nitrotyrosine, an oxidatively-modified protein marker, and cyclooxygenase-2, an inflammatory mediator, were also significantly decreased in the kidneys of the Cirp−/− mice compared to WT mice after RIR. Renal caspase-3 activity was decreased in Cirp−/− mice compared to WT mice after RIR, which corresponded to the reduction of apoptotic cells determined by TUNEL assay. Injection of neutralizing anti-CIRP antibody into WT mice led to an 82% reduction in BUN compared to the vehicle after RIR. Conclusions Deficiency of CIRP results in less renal injury after RIR by attenuating inflammation and oxidative stress. Furthermore, blockade of CIRP shows a protective effect, indicating CIRP as a target in the treatment of RIR.

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Section: Discussionsupporting

confidence: 93%

Deficiency of cold-inducible ribonucleic acid-binding protein reduces renal injury after ischemia-reperfusion

Cen

Yang

Yen

et al. 2016

Surgery

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“…CIRP has been found to be constitutively expressed in low amounts in various tissues and its expression is up regulated during cellular stress (11, 12, 27). The human CIRP gene has been mapped to chromosome locus 19p13.3 and is 95.3% identical to the amino-acid sequence to that of mouse CIRP (10).…”

Section: Discussionmentioning

confidence: 99%

Blocking Cold-Inducible RNA-Binding Protein Protects Liver From Ischemia-Reperfusion Injury

Godwin

Yang

Sharma

et al. 2015

Shock

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Cold inducible RNA-binding protein (CIRP) is a nuclear protein which has been recently identified as a novel inflammatory mediator in hemorrhagic shock and sepsis. We hypothesized that CIRP acts as a potent inflammatory mediator in hepatic ischemia-reperfusion (I/R), and thus blocking CIRP protects against I/R-induced liver injury. Male C57BL/6 mice were subjected to 70% hepatic ischemia by microvascular clamping of the hilum of the left and median liver lobes for 60 min, followed by reperfusion. Anti-CIRP antibody (1 mg/kg body weight) or vehicle (normal saline) in 0.2 mL was injected via the internal jugular vein at the beginning of the reperfusion. Blood and liver tissues were collected 24 h after I/R for various measurements and a 10-day survival study was performed. CIRP released into the circulation was significantly increased 24 h after hepatic I/R. Anti-CIRP antibody treatment markedly reduced hepatocellular damage markers and significantly improved the liver microarchitecture. Anti-CIRP also reduced the systemic and local inflammation demonstrated by attenuation in both serum and hepatic levels of interleukin 6. The expression of neutrophil-attracting chemokine as well as liver neutrophil infiltration was reduced by anti-CIRP treatment. Anti-CIRP also dramatically decreased the amount of apoptosis and nitrosative stress, evidenced by decrease in TUNEL staining and inducible nitric oxide synthase and cyclooxygenase-2 levels, respectively. Finally, the 10-day survival rate was increased from 37.5% in the vehicle group to 75% in the anti-CIRP treatment group. Thus, targeting CIRP offers potential therapeutic implications in the treatment of hepatic I/R injury.

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“…CIRBP is a novel damage associated molecular pattern (DAMP) that induces inflammation in mice (Qiang et al, 2013). Ischemic brain injury is reduced in CIRBP KOs (Zhou et al, 2014). In contrast, RBM3 appears to be a potent neuroprotective protein.…”

Section: Introductionmentioning

confidence: 99%

Cold stress protein RBM3 responds to temperature change in an ultra-sensitive manner in young neurons

et al. 2015

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Extremely mild hypothermia to 36.0°C is not thought to appreciably differ clinically from 37.0°C. However, it is possible that 36.0°C stimulates highly sensitive hypothermic signaling mechanism(s) and alters biochemistry. To the best of our knowledge, no such ultra-sensitive pathway/mechanisms have been described. Here we show that cold stress protein RNA Binding motif 3 (RBM3) increases in neuron and astrocyte cultures maintained at 33°C or 36°C for 24 or 48h, compared to 37°C controls. Neurons cultured at 36°C also had increased global protein synthesis (GPS). Finally, we found that melatonin or fibroblast growth factor 21 (FGF21) augmented RBM3 upregulation in young neurons cooled to 36°C. Our results show that a 1°C reduction in temperature can induce pleiotropic biochemical changes by upregulating GPS in neurons which may be mediated by RBM3 and that this process can be pharmacologically mimicked and enhanced with melatonin or FGF21.

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Cold-inducible RNA-binding protein mediates neuroinflammation in cerebral ischemia

Cited by 87 publications

References 39 publications

Deficiency of cold-inducible ribonucleic acid-binding protein reduces renal injury after ischemia-reperfusion

Deficiency of cold-inducible ribonucleic acid-binding protein reduces renal injury after ischemia-reperfusion

Blocking Cold-Inducible RNA-Binding Protein Protects Liver From Ischemia-Reperfusion Injury

Cold stress protein RBM3 responds to temperature change in an ultra-sensitive manner in young neurons

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