Endothelial-specific Crif1 deletion induces BBB maturation and disruption via the alteration of actin dynamics by impaired mitochondrial respiration

被引：21

作者：

Lee, Min Joung ^{[1
,2
,3
]}

Jang, Yunseon ^{[1
,2
,3
]}

Han, Jeongsu ^{[1
,2
]}

Kim, Soo J. ^{[1
,2
,3
]}

Ju, Xianshu ^{[1
,3
]}

Lee, Yu Lim ^{[1
,3
]}

Cui, Jianchen ^{[1
,3
]}

Zhu, Jiebo ^{[1
,2
,3
]}

Ryu, Min Jeong ^{[2
]}

Choi, Song-Yi ^{[4
]}

Chung, Woosuk ^{[1
,5
,6
]}

Heo, Chaejeong ^{[7
,8
]}

Yi, Hyon-Seung ^{[9
]}

Kim, Hyun Jin ^{[9
]}

Huh, Yang H. ^{[10
]}

Chung, Sookja K. ^{[11
]}

Shong, Minho ^{[9
,12
]}

Kweon, Gi-Ryang ^{[1
,2
]}

Heo, Jun Young ^{[1
,2
,3
]}

机构：

[1] Chungnam Natl Univ, Dept Med Sci, Daejeon, South Korea

[2] Chungnam Natl Univ, Dept Biochem, Daejeon, South Korea

[3] Chungnam Natl Univ, Coll Med, Infect Control Convergence Res Ctr, Daejeon, South Korea

[4] Chungnam Natl Univ, Dept Pathol, Daejeon, South Korea

[5] Chungnam Natl Univ, Sch Med, Dept Anesthesiol & Pain Med, Daejeon, South Korea

[6] Chungnam Natl Univ Hosp, Dept Anesthesiol & Pain Med, Daejeon, South Korea

[7] IBS, Ctr Integrated Nanostruct Phys CINAP, Suwon, South Korea

[8] IBS, CNIR, Suwon, South Korea

[9] Chungnam Natl Univ Hosp, Dept Internal Med, Daejeon, South Korea

[10] Korea Basic Sci Inst, Electron Microscopy Res Ctr, Cheongju, Chungcheongbukd, South Korea

[11] Macau Univ Sci & Technol, Med Fac, Taipa, Macao, Peoples R China

[12] Chungnam Natl Univ, Res Ctr Endocrine & Metab Dis, Sch Med, Daejeon, South Korea

来源：

JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM | 2020年 / 40卷 / 07期

基金：

新加坡国家研究基金会;

关键词：

Crif1; endothelial cells; mitochondrial OxPhos; ATP depletion; blood-brain barrier; BLOOD-BRAIN-BARRIER; TIGHT JUNCTIONS; OXIDATIVE STRESS; CELLS; CYCLOOXYGENASE; RECOMBINATION; DEMYELINATION; ANGIOGENESIS; PERMEABILITY; EXPRESSION;

D O I：

10.1177/0271678X19900030

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Cerebral endothelial cells (ECs) require junctional proteins to maintain blood-brain barrier (BBB) integrity, restricting toxic substances and controlling peripheral immune cells with a higher concentration of mitochondria than ECs of peripheral capillaries. The mechanism underlying BBB disruption by defective mitochondrial oxidative phosphorylation (OxPhos) is unclear in a mitochondria-related gene-targeted animal model. To assess the role of EC mitochondrial OxPhos function in the maintenance of the BBB, we developed an EC-specific CR6-interactin factor1 (Crif1) deletion mouse. We clearly observed defects in motor behavior, uncompacted myelin and leukocyte infiltration caused by BBB maturation and disruption in this mice. Furthermore, we investigated the alteration in the actin cytoskeleton, which interacts with junctional proteins to support BBB integrity. Loss of Crif1 led to reorganization of the actin cytoskeleton and a decrease in tight junction-associated protein expression through an ATP production defect in vitro and in vivo. Based on these results, we suggest that mitochondrial OxPhos is important for the maturation and maintenance of BBB integrity by supplying ATP to cerebral ECs.

引用

页码：1546 / 1561

页数：16

共 2 条

[1] Endothelial-specific Crif1 deletion induces BBB maturation and disruption via the alteration of actin dynamics by impaired mitochondrial respiration (vol 17, pg 315, 2020)
Lee, M. Joung
Jang, Y.
Han, J.
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 2020, 40 (07): : 1562 - 1562
[2] Crif1 deficiency in endothelial cells induces BBB disruption accompanying myelin damage
Lee, M. J.
Jang, Y.
Han, J.
Kim, S. J.
Ju, X.
Lee, Y. L.
Son, J. H.
Cui, J.
Ryu, M. J.
Choi, S. -Y.
Chung, W.
Heo, C.
Huh, Y. H.
Kweon, G. R.
Heo, J. Y.
GLIA, 2019, 67 : E527 - E528

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