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Publication : Matrix metalloproteinase-8 regulates transforming growth factor-β1 levels in mouse tongue wounds and fibroblasts in vitro.

First Author  Aström P Year  2014
Journal  Exp Cell Res Volume  328
Issue  1 Pages  217-27
PubMed ID  25036555 Mgi Jnum  J:217568
Mgi Id  MGI:5614544 Doi  10.1016/j.yexcr.2014.07.010
Citation  Astrom P, et al. (2014) Matrix metalloproteinase-8 regulates transforming growth factor-beta1 levels in mouse tongue wounds and fibroblasts in vitro. Exp Cell Res 328(1):217-27
abstractText  Matrix metalloproteinase-8 (MMP-8)-deficient mice (Mmp8-/-) exhibit delayed dermal wound healing, but also partly contradicting results have been reported. Using the Mmp8-/- mice we investigated the role of MMP-8 in acute wound healing of the mobile tongue, and analyzed the function of tongue fibroblasts in vitro. Interestingly, in the early phase the tongue wounds of Mmp8-/- mice healed faster than those of wild type (wt) mice resulting in significant difference in wound widths (P=0.001, 6-24h). The Mmp8-/- wounds showed no change in myeloperoxidase positive myeloid cell count, but the level of transforming growth factor (TGF)-beta1 was significantly increased (P=0.007) compared to the wt tongues. Fibroblasts cultured from wt tongues expressed MMP-8 and TGF-beta1. However, higher TGF-beta1 levels were detected in Mmp8-/- fibroblasts, and MMP-8 treatment decreased phosphorylated Smad-2 levels and alpha-smooth muscle actin expression in these fibroblasts suggesting reduced TGF-beta1 signaling. Consistently, a degradation of recombinant TGF-beta1 by MMP-8 decreased its ability to activate the signaling cascade in fibroblasts. Moreover, collagen gels with Mmp8-/- fibroblasts reduced more in size. We conclude that MMP-8 regulates tongue wound contraction rate and TGF-beta1 levels. In vitro analyses suggest that MMP-8 may also play a role in regulating TGF-beta1 signaling of stromal fibroblasts.
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