Cardiotrophin-1 is an essential factor in the natural defense of the liver against apoptosis.

Unlabelled: We previously reported that exogenous cardiotrophin-1 (CT-1), a member of the IL-6 family of cytokines, exerts hepatoprotective effects. Because CT-1 is expressed in the normal liver, we hypothesized that this cytokine may constitute an endogenous defense of the liver against proapoptotic stimuli. Here, we found that CT-1-/- mice died faster than wild-type animals after challenge with a lethal dose of the Fas agonist Jo-2.

Cardiotrophin-1 defends the liver against ischemia-reperfusion injury and mediates the protective effect of ischemic preconditioning.

Ischemia-reperfusion (I/R) liver injury occurs when blood flow is restored after prolonged ischemia. A short interruption of blood flow (ischemic preconditioning [IP]) induces tolerance to subsequent prolonged ischemia through ill-defined mechanisms. Cardiotrophin (CT)-1, a cytokine of the interleukin-6 family, exerts hepatoprotective effects and activates key survival pathways like JAK/STAT3.

The lack of cardiotrophin-1 alters expression of interleukin-6 and leukemia inhibitory factor mRNA but does not impair cardiac injury response.

Cardiotrophin-1 (CT-1) was identified as a growth factor for cardiac myocytes and CT-1 protects myocytes from cell death. Adult CT-1(-/-) mice exhibit neural deficits including the loss of preganglionic sympathetic neurons, but their autonomic and cardiac parameters have not been examined. We used these mice to determine if the absence of CT-1 or loss of preganglionic sympathetic input altered heart rate, left ventricular pressure, cardiac contractility (dP/dt), or cell death following ischemia-reperfusion.

Triple knock-out of CNTF, LIF, and CT-1 defines cooperative and distinct roles of these neurotrophic factors for motoneuron maintenance and function.

Members of the ciliary neurotrophic factor (CNTF)-leukemia inhibitory factor (LIF) gene family play an essential role for survival of developing and postnatal motoneurons. When subunits of the shared receptor complex are inactivated by homologous recombination, the mice die at approximately birth and exhibit reduced numbers of motoneurons in the spinal cord and brainstem nuclei. However, mice in which cntf, lif, or cardiotrophin-1 (ct-1) are inactivated can survive and show less motoneuron cell loss.

BMP signaling initiates a neural crest differentiation program in embryonic rat CNS stem cells.

Bone morphogenetic proteins (BMPs) have an important role in neuronal and astrocytic differentiation of embryonic and adult neural stem cells (NSCs). Here, we show that BMP6, BMP7, GDF5, and GDF6 instructively differentiate E12, E14, and E17 rat cortical NSCs into a variety of neural crest lineages. Clonal analysis shows that BMP7-treated NSCs develop mostly into smooth muscle and peripheral glia.

Identification of Wnt responsive genes using a murine mammary epithelial cell line model system.

Background: The Wnt/Wg pathway plays an important role in the developmental program of many cells and tissues in a variety of organisms. In addition, many Wnts and components of their downstream signaling pathways, such as beta-catenin and APC, have been implicated in tumorigenesis. Over the past years, several genes have been identified as Wnt responsive, including c-myc, siamois, and cyclin D1.

Cardiotrophin-1 and urocortin cause protection by the same pathway and hypertrophy via distinct pathways in cardiac myocytes.

Cardiotrophin-1 (CT-1) is an Interleukin-6 family cytokine with known hypertrophic and protective effects in cardiac cells. CT-1 and the corticotrophin releasing hormone-like hormone urocortin protect cardiac myocytes by the same p42/44 mitogen activated protein kinase (p42/44 MAPK) dependent pathway. We investigated whether urocortin is also hypertrophic in cardiac myocytes and whether it shares a common pathway with CT-1 for this effect.

Cardiotrophin-1 (CT-1) can protect the adult heart from injury when added both prior to ischaemia and at reperfusion.

Objectives: To determine whether the cytokine cardiotrophin-1 (CT-1) can protect the adult heart against ischaemia/reperfusion when added either prior to ischaemia or at reperfusion.

Background: CT-1 has previously been shown to protect cultured embryonic or neonatal cardiocytes from cell death. To assess the therapeutic potential of CT-1, it is necessary to determine whether this effect can be observed in adult cardiac cells both in culture and most importantly in the intact heart.

Increased expression of cardiotrophin-1 during ventricular remodeling in hypertensive rats.

Cardiotrophin-1 (CT-1) stimulates longitudinal myocardial cell hypertrophy. We examined the expression of CT-1, leukemia inhibitory factor (LIF), and gp130 by competitive RT-PCR and Western blotting in Dahl salt-sensitive (DS) rats with a high-salt diet, which showed a distinct transition from left ventricular hypertrophy (LVH) to congestive heart failure (CHF). The expression levels of CT-1 mRNA and protein were significantly increased at the CHF stage compared with the LVH stage and age-matched Dahl salt-resistant (DR) rats (n = 6 for each group).

Synergistic induction of tumor antigens by Wnt-1 signaling and retinoic acid revealed by gene expression profiling.

Novel drug targets can be identified by differential analysis of RNA transcripts isolated from cancer cell lines and tissues. We have extended this approach by analyzing differences in gene expression resulting from the drug treatment of transformed and nontransformed cells. A mouse mammary epithelial cell line (C57MG), which conditionally expresses the Wnt-1 proto-oncogene, was left untreated or treated with retinoic acid in the presence or absence of Wnt-1 expression.