Regulation of RhoA by STAT3 coordinates glial scar formation.

Autor:	Renault-Mihara F; Department of Physiology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan frenaultpro@yahoo.fr., Mukaino M; Department of Rehabilitation Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan., Shinozaki M; Department of Physiology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan., Kumamaru H; Department of Orthopedic Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan., Kawase S; Department of Physiology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan., Baudoux M; Department of Physiology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan., Ishibashi T; Department of Physiology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.; Department of Orthopedic Surgery, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan., Kawabata S; Department of Orthopedic Surgery, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan., Nishiyama Y; Department of Orthopedic Surgery, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan., Sugai K; Department of Orthopedic Surgery, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan., Yasutake K; Department of Orthopedic Surgery, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan., Okada S; Department of Advanced Medical Initiatives, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan., Nakamura M; Department of Orthopedic Surgery, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan., Okano H; Department of Physiology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan hidokano@a2.keio.jp.
Jazyk:	angličtina
Zdroj:	The Journal of cell biology [J Cell Biol] 2017 Aug 07; Vol. 216 (8), pp. 2533-2550. Date of Electronic Publication: 2017 Jun 22.
DOI:	10.1083/jcb.201610102
Abstrakt:	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. (© 2017 Renault-Mihara et al.)
Databáze:	MEDLINE
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