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

Masamitsu Hara Department of Advanced Medical Initiatives, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

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.

Masamitsu Hara1,2, Kazu Kobayakawa2 , Yasuyuki Ohkawa3 , Hiromi Kumamaru2, Kazuya Yokota2, Takeyuki Saito1,2, Ken Kijima1,2, Shingo Yoshizaki1,2, Katsumi Harimaya2, Yasuharu Nakashima2 & Seiji Okada1,2

Nature Medicine (2017) doi:10.1038/nm.4354
Received 29 September 2016 Accepted 14 April 2017 Published online 19 June 2017

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