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Characterization of Src family kinas...

Werdich, Xiang Qi.

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Characterization of Src family kinases as potential targets for intervention in vascular endothelial growth factor-mediated retinal neovascularization.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Characterization of Src family kinases as potential targets for intervention in vascular endothelial growth factor-mediated retinal neovascularization./
作者:	Werdich, Xiang Qi.
面頁冊數:	120 p.
附註:	Source: Dissertation Abstracts International, Volume: 66-04, Section: B, page: 1845.
Contained By:	Dissertation Abstracts International66-04B.
標題:	Biology, Cell. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3171564
ISBN:	0542083620

Characterization of Src family kinases as potential targets for intervention in vascular endothelial growth factor-mediated retinal neovascularization.
Werdich, Xiang Qi.

Characterization of Src family kinases as potential targets for intervention in vascular endothelial growth factor-mediated retinal neovascularization. - 120 p.

Source: Dissertation Abstracts International, Volume: 66-04, Section: B, page: 1845.

Thesis (Ph.D.)--Vanderbilt University, 2005.

Hypoxia inducible vascular endothelial growth factor (VEGF) plays a major role in initiation and regulation of retinal neovascularization, which is the leading cause of severe vision loss and irreversible blindness in developed countries. Src family kinases (SFKs) are involved in a broad spectrum of cellular events. However, their roles in VEGF-mediated pathological retinal angiogenesis are completely unknown. This investigation showed that in vitro SFKs were essential for hypoxia-induced VEGF expression in retinal glial Muller cells, a major source of VEGF secretion during the pathogenesis of retinopathy, and for VEGF signaling in retinal microvascular endothelial cells (RMECs). However, neither process required phosphorylation of the SFK activation loop Tyr416. In addition, in RMECs, coexpressed SFK members Src, Fyn and Yes each displayed distinct properties in the regulation of VEGF-mediated cell events. All three kinases were required for VEGF mitogenic signaling. VEGF-induced cell migration was significantly increased in Fyn-deficient cells and decreased in Yes-deficient cells. Interference of Fyn, but not Src or Yes, impaired VEGF-induced tube formation in RMECs. In vivo, in a rat model of oxygen-induced retinopathy (OIR), a significant increase of SFK Tyr416 phosphorylation was found to be specifically associated with pathological retinal angiogenesis, but not with physiological intraretinal vascularization. Muller cells were identified as the source of the elevated phospho-SFK Tyr416 signal. VEGF expression was also highly increased in these OIR retinas. Intravitreous injection of a selective SFK inhibitor (PP2) significantly reduced retinopathy. These findings indicate that aberrant SFK signaling may be an important factor in the pathogenesis of retinal neovascularization. Increased SFK activity or individual SFK member(s) are potential targets for therapeutic intervention in VEGF-mediated retinopathy.

ISBN: 0542083620Subjects--Topical Terms:

1017686
Biology, Cell.

Characterization of Src family kinases as potential targets for intervention in vascular endothelial growth factor-mediated retinal neovascularization.
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