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자연과학대학
생명과학전공
Journal papers
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Downregulation of Wnt-mediated ROS generation is causally implicated in leprechaunism
Title
Downregulation of Wnt-mediated ROS generation is causally implicated in leprechaunism
Authors
Park J.W.
;
Kuehn H.S.
;
Kim S.Y.
;
Chung K.M.
;
Choi H.
;
Kim M.
;
Kim J.
;
Lee S.Y.
;
Bae D.S.
;
Jin D.-K.
;
Bae Y.S.
Ewha Authors
배윤수
;
이수영
;
김재상
SCOPUS Author ID
배윤수
; 이수영
; 김재상
Issue Date
2010
Journal Title
Molecules and Cells
ISSN
1016-8478
Citation
Molecules and Cells vol. 29, no. 1, pp. 63 - 69
Indexed
SCI; SCIE; SCOPUS; KCI
Document Type
Article
Abstract
Although mutations in the insulin receptor have been causally implicated with leprechaunsim, the full pathophysiology of the syndrome cannot be accounted for by malfunction of this gene alone. We sought to characterize a connection between Wnt-mediated cell signaling and the production of reactive oxygen species (ROS) which revealed a novel mechanistic basis for understanding the pathogenesis of leprechaunism. To identify candidate genes involved in this process, a PCR-based subtractive hybridization was performed. Candidate genes were examined for interaction with the Wnt signaling pathway and ROS generation. We found that Dickkopf 1 (Dkk1), a Wnt inhibitor, is overexpressed in skin fibroblast cells derived from three leprechaunism patients and that the cells showed an impaired response to Wnt2 in terms of β-catenin-Tcf activation. Knockdown of Dkk1 in the patient cell lines rescued Wnt2-mediated Tcf activation. Concerted action of Wnt2 and knockdown of Dkk1 resulted in enhanced Nox4 expression and PDGF-induced ROS generation compared to parental patient cells. Furthermore, we found that NFATc2 was activated in response to Wnt2 stimulation and directly activates Nox4 expression. These data show a crosstalk between Wnt and ROS pathways which in turn provides new mechanistic insights at the molecular level into the pathogenesis of leprechaunism. © 2010 KSMCB.
DOI
10.1007/s10059-010-0017-z
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