科研之友
微信
新浪微博
Facebook
分享链接
摘要
Aim: Recent studies have emphasized the importance of the extracellular microenvironment in modulating cell growth, motility, and signalling. In this study we have evaluated the ability of a fibroblast derived-extracellular matrix (fd-ECM) to regulate type I collagen synthesis and degradation in fibroblasts. Main methods: Fibroblasts were plated on plastic (control) or on fd-ECM and type I collagen synthesis and degradation was evaluated. MTT, western blotting, real time PCR, zymographic analysis and inhibitor assays were utilised to investigate the molecular mechanism of type I collagen regulation by the fd-ECM. Key findings: Fibroblasts plated on fd-ECM showed significant downregulation in the production of type I collagen and COL1A2 messenger ribonucleic acid (mRNA) whilst COL1A1 mRNA remained unchanged. Cells grown on fd-ECM exhibited increased matrix metalloproteases (MMPs) and their corresponding mRNAs. The use of transforming growth factor beta (TGF-beta) and MMP inhibitors showed that the excess COL1A1 polypeptide chains were degraded by the combined action of MMP-1, MMP-2, MMP-9 and cathepsins. Significance: These results show the crucial role played by proteases in regulating extracellular matrix protein levels in the feedback regulation of connective tissue gene expression.
- 出版日期2014-5-8
