CXCL1-Triggered PAD4 Cytoplasmic Translocation Enhances Neutrophil Adhesion through Citrullination of PDIA1

被引：7

作者：

Aoyama, Jiro ^{[1
,2
]}

Osaka, Mizuko ^{[1
,3
]}

Deushi, Michiyo ^{[1
]}

Hosoya, Shoichi ^{[4
]}

Ishigami, Akihito ^{[5
]}

Maehara, Taketoshi ^{[2
]}

Yoshida, Masayuki ^{[1
,6
]}

机构：

[1] Tokyo Med & Dent Univ, Grad Sch Med & Dent Sci, Dept Life Sci & Bioeth, Tokyo, Japan

[2] Tokyo Med & Dent Univ, Grad Sch Med & Dent Sci, Dept Neurosurg, Tokyo, Japan

[3] Tokyo Med & Dent Univ, Grad Sch Med & Dent Sci, Dept Nutr & Metab Cardiovasc Dis, Tokyo, Japan

[4] Tokyo Med & Dent Univ, Inst Res, Res Core, Res Facil Cluster, Tokyo, Japan

[5] Tokyo Metropolitan Inst Gerontol, Res Team Funct Biogerontol, Tokyo, Japan

[6] Tokyo Med & Dent Univ, Grad Sch Med & Dent Sci, Dept Life Sci & Bioeth, 1-5-45 Yushima,Bunkyo Ku, Tokyo 1138519, Japan

来源：

JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS | 2022年 / 29卷 / 09期

关键词：

Vascular inflammation; PAD4; Neutrophil; Citrullination; INTEGRIN; INHIBITOR; GENE; MICE; CRM1;

D O I：

10.5551/jat.63237

中图分类号：

R6 [外科学];

学科分类号：

1002 ; 100210 ;

摘要：

Aims: Vascular inflammation is critical for the development and progression of atherosclerosis. Previously, we reported that neutrophils adhere to the vascular endothelium in low-density lipoprotein receptor null mice fed a high-fat diet through hypercitrullination of histone H3 by peptidylarginine deiminase 4 (PAD4) in neutrophils. However, the involvement of PAD4 and citrullination of proteins other than histone H3 in neutrophil adhesion is not well known. In this study, we investigated the function of PAD4 and identified citrullinated proteins during vascular inflammation. Methods: We pefformed flow assay under physiological flow conditions using differentiated HL-60 (dHL-60) cells stimulated with CXCL1 and human umbilical vein endothelial cells (HUVECs). Furthermore, phalloidin stain for dHL-60 stimulated with CXCL1 to observe F-actin polymerization and immunohistochemistry for the activated 132-integrin was conducted. To identify a target of citrullination in the cytoplasm of dHL-60 cells, liquid chromatography-mass spectrometry (LC-MS/MS) for dHL-60 stimulated with CXCL1 was performed. Results: Inhibition or knockdown of PAD4 significantly decreased adhesion of under physiological flow conditions. Thr-Asp-F-amidine trifluoroacetate salt (TDFA), a PAD4 inhibitor, inhibited cytoplasmic translocation of PAD4 by CXCL1. TDFA or knockdown of PAD4 significantly decreased expression of 13 2-integrin and F-actin polymerization activated by CXCL1. Moreover, LC-MS/MS identified protein disulfide isomerase A1 (PDIA1) as a target of citrullination in the cytoplasm of dHL-60 cells. Knockdown of PDIA1 significantly decreased adhesion of dHL-60 cells to HUVECs, expression of 132-integrin, and F-actin polymerization. Conclusions: Cytoplasmic translocation of PAD4 by CXCL1 induces neutrophil adhesion to vascular endothelial cells and citrullination of PDIA1.

引用

页码：1307 / 1318

页数：12

共 27 条

[21] Plasma Peptidylarginine Deiminase IV Promotes VWF-Platelet String Formation and Accelerates Thrombosis After Vessel Injury [J].

Sorvillo, Nicoletta ;

Mizurini, Daniella M. ;

Coxon, Carmen ;

Martinod, Kimberly ;

Tilvawala, Ronak ;

Cherpokova, Deya ;

Salinger, Ari J. ;

Seward, Robert J. ;

Staudinger, Caleb ;

Weerapana, Eranthie ;

Shapiro, Nathan, I ;

Costello, Catherine E. ;

Thompson, Paul R. ;

Wagner, Denisa D. .

CIRCULATION RESEARCH, 2019, 125 (05) :507-519

[22] Dysregulation of PAD4-mediated citrullination of nuclear GSK3β activates TGF-β signaling and induces epithelial-to-mesenchymal transition in breast cancer cells [J].

Stadler, Sonja C. ;

Vincentc, C. Theresa ;

Fedorov, Victor D. ;

Patsialou, Antonia ;

Cherrington, Brian D. ;

Wakshlag, Joseph J. ;

Mohanan, Sunish ;

Zee, Barry M. ;

Zhang, Xuesen ;

Garcia, Benjamin A. ;

Condeelis, John S. ;

Brown, Anthony M. C. ;

Coonrod, Scott A. ;

Allis, C. David .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2013, 110 (29) :11851-11856

[23] Citrullination of NF-κB p65 promotes its nuclear localization and TLR-induced expression of IL-1β and TNFα [J].

Sun, Bo ;

Dwivedi, Nishant ;

Bechtel, Tyler J. ;

Paulsen, Janet L. ;

Muth, Aaron ;

Bawadekar, Mandar ;

Li, Gang ;

Thompson, Paul R. ;

Shelef, Miriam A. ;

Schiffer, Celia A. ;

Weerapana, Eranthie ;

Ho, I-Cheng .

SCIENCE IMMUNOLOGY, 2017, 2 (12)

[24] Global conformational rearrangements in integrin extracellular domains in outside-in and inside-out signaling [J].

Takagi, J ;

Petre, BM ;

Walz, T ;

Springer, TA .

CELL, 2002, 110 (05) :599-611

[25]

TARELLA C, 1982, CANCER RES, V42, P445

[26] HMG-CoA reductase inhibitor modulates monocyte-endothelial cell interaction under physiological flow conditions in vitro - Involvement of Rho GTPase-dependent mechanism [J].

Yoshida, M ;

Sawada, T ;

Ishii, H ;

Gerszten, RE ;

Rosenzweig, A ;

Gimbrone, MA ;

Yasukochi, Y ;

Numano, F .

ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2001, 21 (07) :1165-1171

[27] Colorectal cancer liver metastatic growth depends on PAD4-driven citrullination of the extracellular matrix [J].

Yuzhalin, A. E. ;

Gordon-Weeks, A. N. ;

Tognoli, M. L. ;

Jones, K. ;

Markelc, B. ;

Konietzny, R. ;

Fischer, R. ;

Muth, A. ;

O'Neill, E. ;

Thompson, P. R. ;

Venables, P. J. ;

Kessler, B. M. ;

Lim, S. Y. ;

Muschel, R. J. .

NATURE COMMUNICATIONS, 2018, 9

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