Interaction of reactive astrocytes with type I collagen induces astrocytic scar formation through the integrin-N-cadherin pathway after spinal cord injury

被引：430

作者：

Hara, Masamitsu ^{[1
,2
]}

Kobayakawa, Kazu ^{[2
]}

Ohkawa, Yasuyuki ^{[3
]}

Kumamaru, Hiromi ^{[2
]}

Yokota, Kazuya ^{[2
]}

Saito, Takeyuki ^{[1
,2
]}

Kijima, Ken ^{[1
,2
]}

Yoshizaki, Shingo ^{[1
,2
]}

Harimaya, Katsumi ^{[2
]}

Nakashima, Yasuharu ^{[2
]}

Okada, Seiji ^{[1
,2
]}

机构：

[1] Kyushu Univ, Grad Sch Med Sci, Dept Adv Med Initiat, Fukuoka, Japan

[2] Kyushu Univ, Grad Sch Med Sci, Dept Orthopaed Surg, Fukuoka, Japan

[3] Kyushu Univ, Med Inst Bioregulat, Div Transcript, Fukuoka, Japan

来源：

NATURE MEDICINE | 2017年 / 23卷 / 07期

关键词：

GLIAL SCAR; UP-REGULATION; STEM-CELLS; EXPRESSION; REGENERATION; RECOVERY; ABLATION; NEUROPROTECTION; DEGENERATION; ASTROGLIOSIS;

D O I：

10.1038/nm.4354

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：

Central nervous system (CNS) injury transforms naive astrocytes into reactive astrocytes, which eventually become scar-forming astrocytes that can impair axonal regeneration and functional recovery. This sequential phenotypic change, known as reactive astrogliosis, has long been considered unidirectional and irreversible. However, we report here that reactive astrocytes isolated from injured spinal cord reverted in retrograde to naive astrocytes when transplanted into a naive spinal cord, whereas they formed astrocytic scars when transplanted into injured spinal cord, indicating the environment-dependent plasticity of reactive astrogliosis. We also found that type I collagen was highly expressed in the spinal cord during the scar-forming phase and induced astrocytic scar formation via the integrin-N-cadherin pathway. In a mouse model of spinal cord injury, pharmacological blockade of reactive astrocyte-type I collagen interaction prevented astrocytic scar formation, thereby leading to improved axonal regrowth and better functional outcomes. Our findings reveal environmental cues regulating astrocytic fate decisions, thereby providing a potential therapeutic target for CNS injury.

引用

页码：818 / +

页数：13

共 61 条

[1] Transforming growth factor-beta 1 promotes re-elongation of injured axons of cultured rat hippocampal neurons [J].