STAT3 is a critical regulator of astrogliosis and scar formation after spinal cord injury.
STAT3 is a critical regulator of astrogliosis and scar formation after spinal cord injury.
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DOI：
10.1523/jneurosci.1709-08.2008
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发表时间：
2008-07-09
期刊：
影响因子：
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通讯作者：
Sofroniew MV
中科院分区：
文献类型：
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作者：
Herrmann JE;Imura T;Song B;Qi J;Ao Y;Nguyen TK;Korsak RA;Takeda K;Akira S;Sofroniew MV
Signaling mechanisms that regulate astrocyte reactivity and scar formation after spinal cord injury (SCI) are not well defined. We used the Cre-loxP system under regulation of the mouse GFAP promoter to conditionally delete the cytokine and growth factor signal transducer, STAT3, from astrocytes. After SCI in GFAP-Cre-Reporter mice, over 99% of spinal cord cells that exhibited Cre activity as detected by reporter protein expression were GFAP-expressing astrocytes. Conditional deletion of STAT3 (STAT3-CKO) from astrocytes in GFAP-Cre-loxP mice was confirmed in vivo and in vitro. In uninjured adult STAT3-CKO mice, astrocytes appeared morphologically similar to those in STAT3+/+ mice except for a partially reduced expression of GFAP. In STAT3+/+ mice, activated STAT3 (pSTAT3) was not detectable in astrocytes in uninjured spinal cord, and pSTAT3 was markedly up regulated after SCI in astrocytes and other cell types near the injury. Mice with STAT3-CKO from astrocytes exhibited attenuated up-regulation of GFAP, failure of astrocyte hypertrophy and pronounced disruption of astroglial scar formation after SCI. These changes were associated with increased spread of inflammation, increased lesion volume and partially attenuated motor recovery over the first 28 days after SCI. These findings indicate that STAT3 signaling is a critical regulator of certain aspects of reactive astrogliosis and provide further evidence that scar-forming astrocytes restrict the spread of inflammatory cells after SCI.
