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Cold-inducible RNA binding protein (CIRP), a novel XTcf-3 specific target gene regulates neural development in Xenopus.

ABSTRACT: BACKGROUND:As nuclear mediators of wnt/beta-catenin signaling, Lef/Tcf transcription factors play important roles in development and disease. Although it is well established, that the four vertebrate Lef/Tcfs have unique functional properties, most studies unite Lef-1, Tcf-1, Tcf-3 and Tcf-4 and reduce their function to uniformly transduce wnt/beta-catenin signaling for activating wnt target genes. In order to discriminate target genes regulated by XTcf-3 from those regulated by XTcf-4 or Lef/Tcfs in general, we performed a subtractive screen, using neuralized Xenopus animal cap explants. RESULTS:We identified cold-inducible RNA binding protein (CIRP) as novel XTcf-3 specific target gene. Furthermore, we show that knockdown of XTcf-3 by injection of an antisense morpholino oligonucleotide results in a general broadening of the anterior neural tissue. Depletion of XCIRP by antisense morpholino oligonucleotide injection leads to a reduced stability of mRNA and an enlargement of the anterior neural plate similar to the depletion of XTcf-3. CONCLUSION:Distinct steps in neural development are differentially regulated by individual Lef/Tcfs. For proper development of the anterior brain XTcf-3 and the Tcf-subtype specific target XCIRP appear indispensable. Thus, regulation of anterior neural development, at least in part, depends on mRNA stabilization by the novel XTcf-3 target gene XCIRP.

SUBMITTER: van Venrooy S

PROVIDER: S-EPMC2527318 | biostudies-literature | 2008 Aug

REPOSITORIES: biostudies-literature

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Cold-inducible RNA binding protein (CIRP), a novel XTcf-3 specific target gene regulates neural development in Xenopus.

van Venrooy Stephanie S Fichtner Dagmar D Kunz Martin M Wedlich Doris D Gradl Dietmar D

BMC developmental biology 20080807

<h4>Background</h4>As nuclear mediators of wnt/beta-catenin signaling, Lef/Tcf transcription factors play important roles in development and disease. Although it is well established, that the four vertebrate Lef/Tcfs have unique functional properties, most studies unite Lef-1, Tcf-1, Tcf-3 and Tcf-4 and reduce their function to uniformly transduce wnt/beta-catenin signaling for activating wnt target genes. In order to discriminate target genes regulated by XTcf-3 from those regulated by XTcf-4 o ...[more]

PMID: 18687117

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Project description:Sepsis is a lethal and complex clinical syndrome caused by infection or suspected infection. Cold-inducible RNA-binding protein (CIRP) is a widely distributed cold-shock protein that plays a proinflammatory role in sepsis and that may induce organ damage. However, clinical studies regarding the use of CIRP for the prognostic evaluation of sepsis are lacking. The purpose of this research was to investigate the prognostic significance of peripheral blood concentrations of CIRP in sepsis. Sepsis was assessed using several common measures, including the Acute Physiology and Chronic Health Evaluation II (APACHE II) score; the Sepsis-related Organ Failure Assessment (SOFA) score; the lactate, serum creatinine, and procalcitonin (PCT) levels; the white blood cell (WBC) count; and the neutrophil ratio (N%).Sixty-nine adult patients with sepsis were enrolled in this study. According to the mortality data from the hospital, 38 patients were survivors, and 31 were nonsurvivors. The plasma levels of the biomarkers were measured and the APACHE II and SOFA scores were calculated within 24 hours of patient enrollment into our study. The CIRP level was measured via ELISA.The plasma level of CIRP was significantly higher in the nonsurvivors than in the survivors (median (IQR) 4.99 (2.37-30.17) ng/mL and 1.68 (1.41-13.90) ng/mL, respectively; p = 0.013). The correlations of the CIRP level with the APACHE II score (r = 0.248, p = 0.040, n = 69), the SOFA score (r = 0.323, p = 0.007, n = 69), the serum creatinine level (r = 0.316, p = 0.008, n = 69), and the PCT level (r = 0.282, p = 0.019, n = 69) were significant. Receiver operator characteristic (ROC) curve analysis showed that the area under the ROC curve (AUC) for the CIRP level was 0.674 (p = 0.013). According to Cox proportional hazards models, the CIRP level independently predicts sepsis mortality. When the CIRP level in the peripheral blood increased by 10 ng/mL, the mortality risk increased by 1.05-fold (p = 0.012). Thus, the CIRP level reflects the degree of renal injury but does not predict the severity of sepsis or organ damage.An elevated plasma concentration of CIRP was significantly associated with poor prognosis among patients with sepsis. Therefore, CIRP is a potential predictor of sepsis prognosis.

Project description:BackgroundAcute ischemic stroke (AIS) is the leading cause of morbidity and mortality among cerebrovascular diseases. While animal studies have suggested a correlation between cold-inducible RNA-binding protein (CIRP) serum levels and the severity and prognosis of cerebral infarction, there has been a lack of research exploring this association in humans with cerebral infarction.Materials and methodsA total of 148 patients diagnosed with AIS within 7 days from symptom onset were included in this study. Comprehensive information regarding the patients' basic demographics, medical history, clinical parameters, the severity of cerebral infarction, and serum CIRP levels was collected. Follow-up data were obtained through telephonic interviews or by reviewing clinical notes for 3 months after the patients were discharged to assess the functional outcomes of treatment.ResultsThe findings of this study demonstrated a significant increase in serum CIRP levels during the early stages of AIS, followed by a gradual decline after 3 days. Significant differences were observed in the serum CIRP levels between the 1-day group and the 4-7 day group (P < 0.0047), as well as between the 2-3 day group and the 4-7 day group (P < 0.0006). Moreover, a significant positive correlation was observed between the serum CIRP levels and the severity of cerebral infarction. Higher serum CIRP levels were associated with more severe National Institutes of Health Stroke Scale scores (P < 0.05) and larger cerebral infarction volumes (P < 0.05). Furthermore, patients with higher serum CIRP levels exhibited poorer modified Rankin scale scores (P < 0.05). These findings indicate that serum CIRP serves as an essential pro-inflammatory mediator and a valuable biomarker for assessing brain injury in patients with AIS.ConclusionThe findings of this study suggest an elevation in serum CIRP levels among patients with AIS. These levels are positively correlated with the severity of AIS and serve as indicators of a poor prognosis. Therefore, CIRP could serve as a target for early clinical intervention while managing AIS, and further research should explore serum CIRP levels as prognostic indicators in AIS.

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Cold-inducible RNA binding protein (CIRP), a novel XTcf-3 specific target gene regulates neural development in Xenopus.

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Cold-inducible RNA binding protein (CIRP), a novel XTcf-3 specific target gene regulates neural development in Xenopus.

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