SARS-CoV-2 infection promotes lung thrombosis by inducing integrinβ3 expression in vascular endothelial cells

被引：0

作者：

Ito, Wataru ^{[1
,2
]}

Sakurai, Yuya ^{[1
,3
]}

Maishi, Nako ^{[1
]}

Takeda, Ryo ^{[1
,4
]}

Teshirogi, Takahito ^{[1
,3
]}

Yu, Li ^{[1
]}

Hida, Yasuhiro ^{[13
,14
]}

Sasaki, Michihito ^{[5
,11
]}

Orba, Yasuko ^{[5
,6
,10
,11
]}

Tsumita, Takuya ^{[1
]}

Watanabe, Haruhisa ^{[8
]}

Iimura, Tadahiro ^{[8
]}

Kubo, Terufumi ^{[9
]}

Toba, Shinsuke ^{[5
,7
]}

Sato, Akihiko ^{[5
,7
,11
]}

Matsuda, Aya ^{[1
]}

Kyuno, Daisuke ^{[9
]}

Osanai, Makoto ^{[9
]}

Ohiro, Yoichi ^{[2
]}

Torigoe, Toshihiko ^{[9
]}

Sawa, Hirofumi ^{[6
,10
,11
]}

Hida, Kyoko ^{[1
,12
]}

机构：

[1] Hokkaido Univ, Fac & Grad Sch Dent Med, Vasc Biol & Mol Pathol, Sapporo, Japan

[2] Hokkaido Univ, Fac & Grad Sch Dent Med, Oral & Maxillofacial Surg, Sapporo, Japan

[3] Hokkaido Univ, Fac & Grad Sch Dent Med, Dent Anesthesiol, Sapporo, Japan

[4] Hokkaido Univ, Fac & Grad Sch Dent Med, Oral Diag & Med, Sapporo, Japan

[5] Hokkaido Univ, Int Inst Zoonosis Control, Div Mol Pathobiol, Sapporo, Japan

[6] Hokkaido Univ, Int Inst Zoonosis Control, Int Collaborat Unit, Sapporo, Japan

[7] Shionogi & Co Ltd, Drug Discovery & Dis Res Lab, Osaka, Japan

[8] Hokkaido Univ, Fac & Grad Sch Dent Med, Sapporo, Japan

[9] Sapporo Med Univ, Sch Med, Dept Pathol, Sapporo, Japan

[10] Hokkaido Univ, One Hlth Res Ctr, Sapporo, Japan

[11] Hokkaido Univ, Inst Vaccine Res & Dev, Sapporo, Japan

[12] Hokkaido Univ, Grad Sch Dent Med, Vasc Biol & Mol Pathol, N13 W7,Kita Ku, Sapporo 0608586, Japan

[13] Fujita Hlth Univ, Bantane Hosp, Dept Thorac Surg, Nagoya, Japan

[14] Fujita Hlth Univ, Sch Med, Dept Adv Thorac Surg, Toyoake, Japan

来源：

SCIENTIFIC REPORTS | 2025年 / 15卷 / 01期

关键词：

SARS-CoV-2; Integrin beta 3; Endothelial cells; Thrombosis; Platelets; ACTIVATION; MIGRATION; COVID-19;

D O I：

10.1038/s41598-025-02784-4

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Severe COVID-19 shows a high incidence of pulmonary thrombosis. However, the molecular mechanism underlying this phenomenon remains unclear. We have performed RNA sequencing of isolated endothelial cells (ECs) from infected mid-aged and young mice. Compared to young mice, Integrin beta 3 (ITGB3) expression levels were higher in ECs of mid-aged mice which showed thrombosis in lungs. SARS-CoV-2 exposure increased the number of adhered platelets on the EC monolayer in vitro. Knockdown of ITGB3 in ECs decreased platelet adhesion to them. Among the molecules known as SARS-CoV-2 receptors, Kringle-containing transmembrane protein 1 contributed to ITGB3 upregulation in ECs by SARS-CoV-2. Histological analysis showed that ITGB3-positive blood vessels were frequently detected not only in infected-mid-aged mouse lungs but also in COVID-19-affected human autopsy lungs. This study suggests that the induction of ITGB3 expression in ECs is one of the mechanisms of thrombosis in severe COVID-19 pneumonia.

引用

页数：15

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