罗亚
车站3
细胞生物学
张力素
内斯汀
STAT蛋白
PTEN公司
化学
胶质瘢痕
星形胶质细胞
信号转导
生物
癌症研究
PI3K/AKT/mTOR通路
神经科学
中枢神经系统
神经干细胞
干细胞
作者
François Renault-Mihara,Masahiko Mukaino,Munehisa Shinozaki,Hiromi Kumamaru,Satoshi Kawase,Matthieu Baudoux,Toshiki Ishibashi,Soya Kawabata,Yuichiro Nishiyama,Keiko Sugai,Kaori Yasutake,Seiji Okada,Masaya Nakamura,Hideyuki Okano
标识
DOI:10.1083/jcb.201610102
摘要
Understanding how the transcription factor signal transducer and activator of transcription–3 (STAT3) controls glial scar formation may have important clinical implications. We show that astrocytic STAT3 is associated with greater amounts of secreted MMP2, a crucial protease in scar formation. Moreover, we report that STAT3 inhibits the small GTPase RhoA and thereby controls actomyosin tonus, adhesion turnover, and migration of reactive astrocytes, as well as corralling of leukocytes in vitro. The inhibition of RhoA by STAT3 involves ezrin, the phosphorylation of which is reduced in STAT3-CKO astrocytes. Reduction of phosphatase and tensin homologue (PTEN) levels in STAT3-CKO rescues reactive astrocytes dynamics in vitro. By specific targeting of lesion-proximal, reactive astrocytes in Nestin-Cre mice, we show that reduction of PTEN rescues glial scar formation in Nestin-Stat3+/− mice. These findings reveal novel intracellular signaling mechanisms underlying the contribution of reactive astrocyte dynamics to glial scar formation.
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