Inhibition of dipeptidyl peptidase 4 regulates microvascular endothelial growth induced by inflammatory cytokines

被引:53
作者
Takasawa, Wataru [1 ]
Ohnuma, Kei [2 ]
Hatano, Ryo [1 ]
Endo, Yuko [1 ]
Dang, Nam H. [3 ]
Morimoto, Chikao [1 ,2 ]
机构
[1] Univ Tokyo, Inst Med Sci, Adv Clin Res Ctr, Div Clin Immunol,Minato Ku, Tokyo 1088369, Japan
[2] Univ Tokyo, Inst Med Sci, Res Hosp, Dept Rheumatol & Allergy,Minato Ku, Tokyo 1088369, Japan
[3] Univ Florida, Div Hematol Oncol, Gainesville, FL 32610 USA
关键词
CD26/dipeptidyl peptidase 4; TNF-alpha; IL-1; beta; Endothelial cell; Vascularization; T-CELL-ACTIVATION; CD26; ANTIGEN; 1F7; IV; ANGIOGENESIS; ASSOCIATION; MIGRATION; BLOOD;
D O I
10.1016/j.bbrc.2010.08.112
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
CD26/DPP-4 is abundantly expressed on capillary of inflamed lesion as well as effector T cells. Recently, CD26/dipeptidyl peptidase 4 (DPP-4) inhibition has been used as a novel oral therapeutic approach for patients with type 2 diabetes. While accumulating data indicate that vascular inflammation is a key feature of both micro- and macro-vascular complications in diabetes, the direct role of CD26/DPP-4 in endothelial biology is to be elucidated. We herein showed that proinflammatory cytokines such as tumor necrosis factor or interleukin-1 reduce expression of CD26 on microvascular endothelial cells, and that genetical or pharmacological inhibition of CD26/DPP-4 enhances endothelial growth both in vitro and in vivo. With DPP-4 inhibitors being used widely in the treatment of type 2 diabetes, our data strongly suggest that DPP-4 inhibition plays a pivotal role in endothelial growth and may have a potential role in the recovery of local circulation following diabetic vascular complications. (C) 2010 Published by Elsevier Inc.
引用
收藏
页码:7 / 12
页数:6
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