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Ephrin-B2 expression in the proprioceptive sensory system.

ABSTRACT: Recent studies have shown that ephrin-B2 on sensory afferent fibers from the dorsal root ganglia (DRG) controls transmission of pain sensation to the spinal cord. We examined ephrin-B2 expression in mouse DRG and spinal cord using an ephrin-B2/ß-galactosidase chimeric allele. We found that ephrin-B2 is expressed exclusively in proprioceptive neurons and fibers in neonates, while expression in lamina III and IV of the adult spinal cord was observed in addition to that in the deeper laminae. We confirmed that ephrin-B2 protein causes co-clustering of EphB2 and glutamate receptors in spinal cord neurons. Our data are consistent with a role for ephrin-B2 in transmission of positional information to the CNS, and thus suggest a role in synaptic plasticity of spinal cord locomotor circuits that are known to be sensitive to proprioceptive sensory input after spinal cord injury.

SUBMITTER: Logan SM

PROVIDER: S-EPMC3867235 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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Ephrin-B2 expression in the proprioceptive sensory system.

Logan Shaun M SM Romero Mario I MI Nguyen Dianna H DH Benson M Douglas MD

Neuroscience letters 20130426

Recent studies have shown that ephrin-B2 on sensory afferent fibers from the dorsal root ganglia (DRG) controls transmission of pain sensation to the spinal cord. We examined ephrin-B2 expression in mouse DRG and spinal cord using an ephrin-B2/ß-galactosidase chimeric allele. We found that ephrin-B2 is expressed exclusively in proprioceptive neurons and fibers in neonates, while expression in lamina III and IV of the adult spinal cord was observed in addition to that in the deeper laminae. We co ...[more]

PMID: 23623938

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Project description:Bone marrow vascular endothelial cells (BM EC) regulate multiple myeloma pathogenesis. Identification of the mechanisms underlying this interaction could lead to the development of improved strategies for treating multiple myeloma. Here, we performed a transcriptomic analysis of human ECs with high capacity to promote multiple myeloma growth, revealing overexpression of the receptor tyrosine kinases, EPHB1 and EPHB4, in multiple myeloma-supportive ECs. Expression of ephrin B2 (EFNB2), the binding partner for EPHB1 and EPHB4, was significantly increased in multiple myeloma cells. Silencing EPHB1 or EPHB4 in ECs suppressed multiple myeloma growth in coculture. Similarly, loss of EFNB2 in multiple myeloma cells blocked multiple myeloma proliferation and survival in vitro, abrogated multiple myeloma engraftment in immune-deficient mice, and increased multiple myeloma sensitivity to chemotherapy. Administration of an EFNB2-targeted single-chain variable fragment also suppressed multiple myeloma growth in vivo. In contrast, overexpression of EFNB2 in multiple myeloma cells increased STAT5 activation, increased multiple myeloma cell survival and proliferation, and decreased multiple myeloma sensitivity to chemotherapy. Conversely, expression of mutant EFNB2 lacking reverse signaling capacity in multiple myeloma cells increased multiple myeloma cell death and sensitivity to chemotherapy and abolished multiple myeloma growth in vivo. Complementary analysis of multiple myeloma patient data revealed that increased EFNB2 expression is associated with adverse-risk disease and decreased survival. This study suggests that EFNB2 reverse signaling controls multiple myeloma pathogenesis and can be therapeutically targeted to improve multiple myeloma outcomes.SignificanceEphrin B2 reverse signaling mediated by endothelial cells directly regulates multiple myeloma progression and treatment resistance, which can be overcome through targeted inhibition of ephrin B2 to abolish myeloma.

Dataset Information

Ephrin-B2 expression in the proprioceptive sensory system.

Publications

Ephrin-B2 expression in the proprioceptive sensory system.

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