HSP70 increases extracellular matrix production by human vascular smooth muscle through TGF-β1 up-regulation
| Autor: | Susana López-Ongil, Diego Rodríguez-Puyol, Viviana Raoch, Laura Calleros, M. Rodriguez-Puyol, Marta González-Ramos, Sergio de Frutos, Mercedes Griera |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
MAPK/ERK pathway
Vascular smooth muscle Myocytes Smooth Muscle Gene Expression Biochemistry Collagen Type I Muscle Smooth Vascular Extracellular matrix Transforming Growth Factor beta1 Downregulation and upregulation Heat shock protein Extracellular Myocyte Humans HSP70 Heat-Shock Proteins Phosphorylation Cells Cultured biology Cell Biology Cell biology Extracellular Matrix Fibronectins Up-Regulation Fibronectin Toll-Like Receptor 4 Transcription Factor AP-1 Gene Expression Regulation biology.protein Mitogen-Activated Protein Kinases Protein Processing Post-Translational |
| Zdroj: | The international journal of biochemistrycell biology. 45(2) |
| ISSN: | 1878-5875 |
| Popis: | The circulating levels of heat shock proteins (HSP) are increased in cardiovascular diseases; however, the implication of this for the fibrotic process typical of such diseases remains unclear. HSP70 can interact with the vascular smooth muscle cells (SMC), the major producer of extracellular matrix (ECM) proteins, through the Toll-like receptors 4 (TLR4). The transforming growth factor type-β1 (TGF-β1) is a well known vascular pro-fibrotic cytokine that is regulated in part by AP-1-dependent transcriptional mechanisms. We hypothesized that extracellular HSP70 could interact with SMCs, inducing TGF-β1 synthesis and subsequent changes in the vascular ECM. We demonstrate that extracellular HSP70 binds to human aorta SMC TLR4, which up-regulates the AP-1-dependent transcriptional activity of the TGF-β1 promoter. This is achieved through the mitogen activated protein kinases JNK and ERK, as demonstrated by the use of specific blockers and the knockdown of TLR4 with specific small interfering RNAs. The TGF-β1 upregulation increase the expression of the ECM proteins type I collagen and fibronectin. This novel observation may elucidate the mechanisms by which HSP70 contributes in the inflammation and fibrosis present in atherosclerosis and other fibrosis-related diseases. |
| Databáze: | OpenAIRE |
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