Syndecan-1 promotes the angiogenic phenotype of multiple myeloma endothelial cells

Angiogenesis is considered a hallmark of multiple myeloma (MM) progression. In the present study, we evaluated the morphological and functional features of endothelial cells (ECs) derived from bone marrow (BM) of patients affected by MM (MMECs). We found that MMECs compared with normal BM ECs (BMECs) showed increased expression of syndecan-1. Silencing of syndecan-1 expression by RNA interference technique decreased in vitro EC survival, proliferation and organization in capillary-like structures. In vivo, in severe combined immunodeficient mice, syndecan-1 silencing inhibited MMEC organization into patent vessels. When overexpressed in human umbilical vein ECs and BMECs, syndecan-1 induced in vitro and in vivo angiogenic effects. Flow-cytometric analysis of MMECs silenced for syndecan-1 expression indicated a decreased membrane expression of vascular endothelial growth factor (VEGF) receptor-2 (VEGFR-2). Immunoprecipitation and confocal analysis showed colocalization of VEGFR-2 with syndecan-1. Absence of nuclear translocation of VEGFR-2 in syndecan-1-knockdown cells together with the shift from perinuclear localization to recycling compartments suggest a role of syndecan-1 in modulation of VEGFR-2 localization. This correlated with an in vitro decreased VEGF-induced invasion and motility. These results suggest that syndecan-1 may contribute to the highly angiogenic phenotype of MMECs by promoting EC proliferation, survival and modulating VEGF–VEGFR-2 signalling

Caveolin-1 Plays a Crucial Role in Inhibiting Neuronal Differentiation of Neural Stem/Progenitor Cells via VEGF Signaling-Dependent Pathway

In the present study, we aim to elucidate the roles of caveolin-1(Cav-1), a 22 kDa protein in plasma membrane invaginations, in modulating neuronal differentiation of neural progenitor cells (NPCs). In the hippocampal dentate gyrus, we found that Cav-1 knockout mice revealed remarkably higher levels of vascular endothelial growth factor (VEGF) and the more abundant formation of newborn neurons than wild type mice. We then studied the potential mechanisms of Cav-1 in modulating VEGF signaling and neuronal differentiation in isolated cultured NPCs under normoxic and hypoxic conditions. Hypoxic embryonic rat NPCs were exposed to 1% O2 for 24 h and then switched to 21% O2 for 1, 3, 7 and 14 days whereas normoxic NPCs were continuously cultured with 21% O2. Compared with normoxic NPCs, hypoxic NPCs had down-regulated expression of Cav-1 and up-regulated VEGF expression and p44/42MAPK phosphorylation, and enhanced neuronal differentiation. We further studied the roles of Cav-1 in inhibiting neuronal differentiation by using Cav-1 scaffolding domain peptide and Cav-1-specific small interfering RNA. In both normoxic and hypoxic NPCs, Cav-1 peptide markedly down-regulated the expressions of VEGF and flk1, decreased the phosphorylations of p44/42MAPK, Akt and Stat3, and inhibited neuronal differentiation, whereas the knockdown of Cav-1 promoted the expression of VEGF, phosphorylations of p44/42MAPK, Akt and Stat3, and stimulated neuronal differentiation. Moreover, the enhanced phosphorylations of p44/42MAPK, Akt and Stat3, and neuronal differentiation were abolished by co-treatment of VEGF inhibitor V1. These results provide strong evidence to prove that Cav-1 can inhibit neuronal differentiation via down-regulations of VEGF, p44/42MAPK, Akt and Stat3 signaling pathways, and that VEGF signaling is a crucial target of Cav-1. The hypoxia-induced down-regulation of Cav-1 contributes to enhanced neuronal differentiation in NPCs

Razão e emoção: uma leitura analítico-comportamental de avanços recentes nas neurociências Reason and emotion: a behavior-analytic interpretation of recent advances in neurosciences

Achados recentes das neurociências apresentam uma visão integrada do funcionamento humano que envolve a presença de relações entre os grandes sistemas orgânicos, entre estados fisiológicos e cognitivos e entre razão e emoção. Este artigo objetiva contrastar tais estudos a aspectos centrais do modelo interpretativo skinneriano, destacando o papel de relações entre processos respondentes e operantes para a compreensão da interdependência entre razão e emoção. Investiga-se a importância de respostas emocionais e do comportamento verbal para a expressão de respostas tidas como racionais e, de uma maneira geral, para a seleção do repertório comportamental, verbal e não-verbal. Ressalta-se que o atual movimento de superação de propostas dualistas de compreensão do ser humano pelas neurociências aproxima-se da perspectiva analítico-comportamental de investigação de respostas abertas e encobertas no contexto de relações indivíduo-ambiente.<br>Recent findings of the neurosciences present an integrated view of the human functioning, one that encompasses the relationships among the great organic systems, between physiological and cognitive states and between reason and emotion. The aim of this paper is to contrast such studies with central aspects of the Skinnerian explanatory system, highlighting the role of relations between respondent and operant processes for an understanding of the interdependence between reason and emotion. The importance of emotional responses and verbal behavior for rational responding and, moreover, for the selection of verbal and non-verbal behavioral repertoire, is discussed. It is argued that the current movement in the neurosciences towards overcoming dualistic views of the human being is compatible with the behavior-analytic approach to overt and covert responses in the context of individual-environment relations