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Title 

The WNT antagonist Dickkopf2 promotes angiogenesis in rodent and human endothelial cells

 

혈관 내피분화에 있어 DKK2의 새로운 기능 규명

Authors 

Jeong-Ki MinH ParkH J ChoiY KimB J PyunV AgrawalB W SongJ JeonY S MaengS S RhoS ShimJ H ChaiB K KooH J HongC O YunC ChoiY M KimK C HwangY G Kwon

Publisher 

American Society for Clinical Investigation

Issue Date 

2011

Citation 

Journal of Clinical Investigation, vol. 121, no. 5, pp. 1882-1893

Abstract 

Neovessel formation is a complex process governed by the orchestrated action of multiple factors that regulate EC specification and dynamics within a growing vascular tree. These factors have been widely exploited to develop therapies for angiogenesis-related diseases such as diabetic retinopathy and tumor growth and metastasis. WNT signaling has been implicated in the regulation and development of the vascular system, but the detailed mechanism of this process remains unclear. Here, we report that Dickkopf1 (DKK1) and Dickkopf2 (DKK2), originally known as WNT antagonists, play opposite functional roles in regulating angiogenesis. DKK2 induced during EC morphogenesis promoted angiogenesis in cultured human endothelial cells and in in vivo assays using mice. Its structural homolog, DKK1, suppressed angiogenesis and was repressed upon induction of morphogenesis. Importantly, local injection of DKK2 protein significantly improved tissue repair, with enhanced neovascularization in animal models of both hind limb ischemia and myocardial infarction. We further showed that DKK2 stimulated filopodial dynamics and angiogenic sprouting of ECs via a signaling cascade involving LRP6-mediated APC/Asef2/Cdc42 activation. Thus, our findings demonstrate the distinct functions of DKK1 and DKK2 in controlling angiogenesis and suggest that DKK2 may be a viable therapeutic target in the treatment of ischemic vascular diseases.

ISSN 

0021-9738

Link 

http://dx.doi.org/10.1172/JCI42556

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2017-04-19


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