The TGF-β1-Induced Expression of Matrix Metalloproteinases in Mesenchymal Stromal Cells is Influenced by Type of Substrate
- Corresponding Author:
- Dr. Wilhelm K. Aicher
ZMF Research Laboratories
Center for Regenerative Biology and Medicine & Department of Orthopaedic Surgery
University of Tübingen Medical School
Waldhoernle Strasse 22, D 72072
Tel: x49 7071 298 6045
Fax: x49 7071 29 4637
E-mail: [email protected]
Received date: July 06, 2011; Accepted date: October 27, 2011; Published date: October 29, 2011
Citation: Warstat K, Felka T, Mittag F, Kluba T, Rolauffs B, et al. (2011) The TGF- β1-Induced Expression of Matrix Metalloproteinases in Mesenchymal Stromal Cells is Influenced by Type of Substrate. J Tissue Sci Eng 2:108. doi:10.4172/2157-7552.1000108
Copyright: © 2011 Warstat K, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Transforming growth factor (TGF)-?1 activates the expression of matrix metalloproteinases (MMPs) in fibroblasts. Attachment of these cells to laminin-111 further raises the TGF-?1-induced expression of MMP-3 and MMP-10. Mesenchymal stromal cells (MSC) attach to a variety of extracellular matrix proteins during development and wound healing. We therefore investigated the TGF-?1-regulated expression of MMPs in MSC upon attachment to laminin-111 and type I collagen. The expression of MMPs was determined by quantitative reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay. The TGF-?1 signalling pathways were investigated by immunoblot and by pharmacological blocking of Smad2, MEK/ERK and p38MAPK activities. Overall, TGF-?1 significantly activated the expression of mRNA encoding MMP-3 (p=0.05), MMP-13 (p=0.05) and TIMP-1 (p=0.01) in MSC. Induction of MMP-10 was not significant. In contrast to our observation on fibroblasts, the attachment of MSC to laminin-111 did not affect the TGF-?1-induced expression of MMP-3 and MMP-10. Attachment to type I collagen reduced the TGF-?1-induced secretion of MMP-3 and MMP-10 compared to cells grown on laminin-111 or tissue culture plastic dishes. The expression of MMP-3 was induced by TGF-?1 via Smad2, ERK1/2 and p38MAPK. The expression of MMP-10 was regulated by Smad2 and ERK/1/2, whereas the expression of MMP-13 was shown to be p38 MAPkinase dependent. We conclude that the regulation of MMP-3, MMP-10, and MMP-13 by TGF-?1 proceeds via distinct signalling routes. In contrast to the regulatory pathways in fibroblasts, we could not prove a co-signalling of TGF-?1- and integrin-dependent pathways for the regulation of MMP-3 and MMP-10 in MSC upon attachment to laminin-111. Therefore, MSC respond differently to TGF-?1 and extracellular matrix molecules compared to fibroblasts.