Tryptophan 387 and 390 residues in ADAMTS13 are crucial to the ability of vascular tube formation and cell migration of endothelial cells

被引：2

作者：

Liu, Ling ^{[1
]}

Ma, Zhenni ^{[2
,3
]}

Zhou, Xuemei ^{[4
]}

Yin, Jie ^{[2
,3
]}

Lu, Jun ^{[4
]}

Su, Jian ^{[2
,3
]}

Shen, Fei ^{[2
,3
]}

Xie, Liqian ^{[2
,3
]}

Hu, Shaoyan ^{[4
]}

Ling, Jing ^{[4
]}

机构：

[1] Soochow Univ, Clin Med Res Ctr Jiangsu Prov, Dept Orthoped, Affiliated Hosp 1, Suzhou, Peoples R China

[2] Soochow Univ, Jiangsu Inst Hematol, Key Lab Thrombosis & Hemostasis, Minist Hlth,Affiliated Hosp 1, Suzhou, Peoples R China

[3] Soochow Univ, Collaborat Innovat Ctr Hematol, Suzhou, Peoples R China

[4] Soochow Univ, Dept Hematol & Oncol, Childrens Hosp, 92 Zhongnan St, Suzhou 215006, Peoples R China

来源：

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY | 2020年 / 47卷 / 08期

基金：

中国国家自然科学基金;

关键词：

ADAMTS13; endothelial cells; migration; proliferation; WXXW motif; VON-WILLEBRAND-FACTOR; SPACER DOMAIN; VEGF; MUTATIONS; VWF; ANGIOGENESIS; EXPRESSION; SECRETION; CLEAVAGE; GENE;

D O I：

10.1111/1440-1681.13313

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

A disintegrin and metalloproteinase with thrombospondin motifs 13 (ADAMTS13) was mainly generated and secreted from endothelial cells (ECs). Our previous study showed that tryptophan (Trp) residues at 387 and 390 in ADAMTS13 are required for its secretion and enzymatic activity. However, the effects on its host cell as well as the potential mechanism have not been clear. The aim of the study was to examine the effects of Trp residues 387 and 390 of ADAMTS13 on the biological processes of ECs. Herein, Trp was substituted with alanine in ADAMTS13 to generate ADAMTS13 mutants at 387 (W387A), 390 (W390A), and double mutants at 387 and 390 (2WA), respectively. We found that substitution mutation impaired vascular endothelial growth factor (VEGF) secretion and the downstream JAK1/STAT3 activation, the binding ability to Von Willebrand factor, cell proliferation, migration, and vascular tube formation. Overall, our study concluded that Trp(387) and Trp(390) of ADAMTS13 play vital roles in the biological function of ECs.

引用

页码：1402 / 1409

页数：8

共 43 条

[1] The proximal carboxyl-terminal domains of ADAMTS13 determine substrate specificity and are all required for cleavage of von Willebrand factor [J].