MMP2 is an effector of STAT3 exclusively during the proteolytic migration of astrocytes. (A) Real-time quantitative PCR analysis show that MMP2 mRNA is significantly reduced in STAT3-CKO astrocytes in usual culture conditions, whereas MMP9 is unchanged. Normalization is made with GAPDH, Mann-Whitney U test, n = 5 per group; **, P < 0.005. (B) MMP2 mRNA is also significantly lower in STAT3-CKO astrocytes versus WT astrocytes after challenge with LPA or wound scratch. (Normalization is made with GAPDH, Mann-Whitney U test, n = 5 per group). (C) Gelatin zymography of medium conditioned by astrocytes indicates significantly reduced secretion of MMP2 by STAT3-CKO astrocytes when compared with WT astrocytes (Mann-Whitney U test, n = 3). (D) STAT3-CKO astrocytes exhibit defective invasion through Matrigel, and reduced invasion of MMP2-KO astrocytes confirmed that MMP2 is necessary for invasion through Matrigel. (E) In contrast with STAT3-CKO astrocytes, MMP2-KO astrocytes do not show any significant reduction in migration in a trans-well assay compared with WT astrocytes, indicating that MMP2 does not affect nonproteolytic migration in this assay and suggesting the existence of other effectors of STAT3 involved in the nonproteolytic migration of astrocytes. *, P < 0.05; ns, not significant. Error bars indicate ±SEM.