Conditional ablation of Stat3 or Socs3 discloses a dual role for reactive astrocytes after spinal cord injury

被引：785

作者：

Seiji Okada ^{[1
]}

Masaya Nakamura ^{[2
]}

Hiroyuki Katoh ^{[3
]}

Tamaki Miyao ^{[4
]}

Takuya Shimazaki ^{[4
]}

Ken Ishii ^{[1
]}

Junichi Yamane ^{[1
]}

Akihiko Yoshimura ^{[4
]}

Yukihide Iwamoto ^{[1
]}

Yoshiaki Toyama ^{[4
]}

Hideyuki Okano ^{[5
]}

机构：

[1] Department of Physiology, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582

[2] Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582

[3] Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology, Kawaguchi, Saitama 332-0012

[4] Department of Orthopaedic Surgery, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582

[5] Division of Molecular and Cellular Immunology, Medical Institute of Bioregulation, Kyushu University, Higashi-ku, Fukuoka 812-8582

来源：

Nature Medicine | 2006年 / 12卷 / 7期

关键词：

D O I：

10.1038/nm1425

中图分类号：

学科分类号：

摘要：

In the injured central nervous system (CNS), reactive astrocytes form a glial scar and are considered to be detrimental for axonal regeneration, but their function remains elusive. Here we show that reactive astrocytes have a crucial role in wound healing and functional recovery by using mice with a selective deletion of the protein signal transducer and activator of transcription 3 (Stat3) or the protein suppressor of cytokine signaling 3 (Socs3) under the control of the Nes promoter-enhancer (Nes-Stat3-/-, Nes-Socs3-/-). Reactive astrocytes in Nes-Stat3-/- mice showed limited migration and resulted in markedly widespread infiltration of inflammatory cells, neural disruption and demyelination with severe motor deficits after contusive spinal cord injury (SCI). On the contrary, we observed rapid migration of reactive astrocytes to seclude inflammatory cells, enhanced contraction of lesion area and notable improvement in functional recovery in Nes-Socs3-/- mice. These results suggest that Stat3 is a key regulator of reactive astrocytes in the healing process after SCI, providing a potential target for intervention in the treatment of CNS injury. © 2006 Nature Publishing Group.

引用

页码：829 / 834

页数：5