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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Kinin-B2 Receptor Activity Determines the Differentiation Fate of Neural Stem Cells

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Author(s):
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Trujillo, Cleber A. [1] ; Negraes, Priscilla D. [1] ; Schwindt, Telma T. [1] ; Lameu, Claudiana [1] ; Carromeu, Cassiano [2, 3] ; Muotri, Alysson R. [2, 3] ; Pesquero, Joao B. [4] ; Cerqueira, Debora M. [5] ; Pillat, Micheli M. [1] ; de Souza, Hellio D. N. [1] ; Turaca, Lauro T. [4] ; Abreu, Jose G. [5] ; Ulrich, Henning [1]
Total Authors: 13
Affiliation:
[1] Univ Sao Paulo, Inst Quim, Dept Bioquim, BR-05508000 Sao Paulo - Brazil
[2] Univ Calif San Diego, Dept Pediat, San Diego, CA 92093 - USA
[3] Univ Calif San Diego, Dept Cellular & Mol Med, San Diego, CA 92093 - USA
[4] Univ Fed Sao Paulo, Dept Biofis, BR-04023062 Sao Paulo - Brazil
[5] Univ Fed Rio de Janeiro, Inst Ciencias Biomed, BR-21941902 Rio De Janeiro - Brazil
Total Affiliations: 5
Document type: Journal article
Source: Journal of Biological Chemistry; v. 287, n. 53, p. 44046-44061, DEC 28 2012.
Web of Science Citations: 24
Abstract

Bradykinin is not only important for inflammation and blood pressure regulation, but also involved in neuromodulation and neuroprotection. Here we describe novel functions for bradykinin and the kinin-B2 receptor (B2BkR) in differentiation of neural stem cells. In the presence of the B2BkR antagonist HOE-140 during rat neurosphere differentiation, neuron-specific beta 3-tubulin and enolase expression was reduced together with an increase in glial protein expression, indicating that bradykinin- induced receptor activity contributes to neurogenesis. In agreement, HOE-140 affected in the same way expression levels of neural markers during neural differentiation of murine P19 and human iPS cells. Kinin-B1 receptor agonists and antagonists did not affect expression levels of neural markers, suggesting that bradykinin-mediated effects are exclusively mediated via B2BkR. Neurogenesis was augmented by bradykinin in the middle and late stages of the differentiation process. Chronic treatment with HOE-140 diminished eNOS and nNOS as well as M1-M4 muscarinic receptor expression and also affected purinergic receptor expression and activity. Neurogenesis, gliogenesis, and neural migration were altered during differentiation of neurospheres isolated from B2BkR knock-out mice. Whole mount in situ hybridization revealed the presence of B2BkR mRNA throughout the nervous system in mouse embryos, and less beta 3-tubulin and more glial proteins were expressed in developing and adult B2BkR knock-out mice brains. As a underlying transcriptional mechanism for neural fate determination, HOE-140 induced up-regulation of Notch1 and Stat3 gene expression. Because pharmacological treatments did not affect cell viability and proliferation, we conclude that bradykinin-induced signaling provides a switch for neural fate determination and specification of neurotransmitter receptor expression. (AU)

FAPESP's process: 06/61285-9 - Molecular basis of differentiation of stem and neural progenitor cells
Grantee:Alexander Henning Ulrich
Support Opportunities: Research Projects - Thematic Grants