Antiangiogenic and Antineuroinflammatory Effects of Kallistatin Through Interactions With the Canonical Wnt Pathway

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	Antiangiogenic and Antineuroinflammatory Effects of Kallistatin Through Interactions With the Canonical Wnt Pathway
	Liu, Xiaochen ; Zhang, Bin ; McBride, Jeffrey D. ; Zhou, Kevin ; Lee, Kyungwon ; Zhou, Yueping ; Liu, Zuguo ; Ma, Jian-xing ; Zhou YP(周跃平) ; Liu ZG(刘祖国)
刊名	http://dx.doi.org/10.2337/db12-1710
	2013
关键词	ENDOTHELIAL GROWTH-FACTOR OXYGEN-INDUCED RETINOPATHY VASCULAR-PERMEABILITY FACTOR EPITHELIUM-DERIVED FACTOR RETINAL NEOVASCULARIZATION DIABETIC-RETINOPATHY ANGIOGENIC INHIBITOR TISSUE KALLIKREIN TUMOR-GROWTH MOUSE
英文摘要	National Basic Research Program of China [2011CB504606]; National Institutes of Health [EY018659, EY012231, EY019309, P20GM104934]; Kallistatin is a member of the serine proteinase inhibitor superfamily. Kallistatin levels have been shown to be decreased in the vitreous while increased in the circulation of patients with diabetic retinopathy (DR). Overactivation of the Wnt pathway is known to play pathogenic roles in DR. To investigate the role of kallistatin in DR and in Wnt pathway activation, we generated kallistatin transgenic (kallistatin-TG) mice overexpressing kallistatin in multiple tissues including the retina. In the oxygen-induced retinopathy (OIR) model, kallistatin overexpression attenuated ischemia-induced retinal neovascularization. In diabetic kallistatin-TG mice, kallistatin overexpression ameliorated retinal vascular leakage, leukostasis, and overexpression of vascular endothelial growth factor and intracellular adhesion molecule. Furthermore, kallistatin overexpression also suppressed Wnt pathway activation in the retinas of the OIR and diabetic models. In diabetic Wnt reporter (BAT-gal) mice, kallistatin overexpression suppressed retinal Wnt reporter activity. In cultured retinal cells, kallistatin blocked Wnt pathway activation induced by high glucose and by Wnt ligand. Coprecipitation and ligand-binding assays both showed that kallistatin binds to a Wnt coreceptor LRP6 with high affinity (K-d = 4.5 nmol/L). These observations suggest that kallistatin is an endogenous antagonist of LRP6 and inhibitor of Wnt signaling. The blockade of Wnt signaling may represent a mechanism for its antiangiogenic and antineuroinflammatory effects.
语种	英语
出版者	AMER DIABETES ASSOC
内容类型	期刊论文
源URL	[http://dspace.xmu.edu.cn/handle/2288/93414]
专题	医学院－已发表论文
推荐引用方式 GB/T 7714	Liu, Xiaochen,Zhang, Bin,McBride, Jeffrey D.,et al. Antiangiogenic and Antineuroinflammatory Effects of Kallistatin Through Interactions With the Canonical Wnt Pathway[J]. http://dx.doi.org/10.2337/db12-1710,2013.
APA	Liu, Xiaochen.,Zhang, Bin.,McBride, Jeffrey D..,Zhou, Kevin.,Lee, Kyungwon.,...&刘祖国.(2013).Antiangiogenic and Antineuroinflammatory Effects of Kallistatin Through Interactions With the Canonical Wnt Pathway.http://dx.doi.org/10.2337/db12-1710.
MLA	Liu, Xiaochen,et al."Antiangiogenic and Antineuroinflammatory Effects of Kallistatin Through Interactions With the Canonical Wnt Pathway".http://dx.doi.org/10.2337/db12-1710 (2013).