Angiogenic Property of Hepatocyte Growth Factor Is Dependent on Upregulation of Essential Transcription Factor for Angiogenesis, ets-1
| Autor: | Yoshiaki Taniyama, Hideo Shimizu, Toshio Ogihara, Ryuichi Morishita, Toshikazu Nakamura, Motokuni Aoki, Yasufumi Kaneda, Kunio Matsumoto, Hiromi Koike, Naruya Tomita |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Angiogenesis
medicine.medical_treatment Neovascularization Physiologic Biology Matrix metalloproteinase Muscle Smooth Vascular Proto-Oncogene Protein c-ets-1 Downregulation and upregulation Proto-Oncogene Proteins Physiology (medical) medicine Animals Humans RNA Messenger Transcription factor Cells Cultured Proto-Oncogene Proteins c-ets Hepatocyte Growth Factor Growth factor Transfection Rats Up-Regulation Endothelial stem cell Gene Expression Regulation Cancer research Hepatocyte growth factor Endothelium Vascular Cardiology and Cardiovascular Medicine Transcription Factors medicine.drug |
| Zdroj: | Circulation. 107:1411-1417 |
| ISSN: | 1524-4539 0009-7322 |
| Popis: | Background— Although hepatocyte growth factor (HGF) is an angiogenic growth factor, it is still unclear how it exerts its angiogenic effects. Thus, we focused on the role of an essential transcription factor for angiogenesis, ets-1. In this study, we addressed the following specific questions: (1) what genes responsible for angiogenesis can be regulated by HGF and (2) whether upregulation of gene expression for angiogenesis is dependent on ets-1. Methods and Results— In human endothelial cells, HGF significantly stimulated the matrix-degrading pathway, such as the production of matrix metalloprotease-1 (MMP-1) through its specific receptor, c-met. In addition, HGF also significantly increased HGF itself and its specific receptor, c-met. Moreover, HGF significantly increased the transcription activity and mRNA expression of ets-1 in a time-dependent manner. Importantly, transfection of antisense ets-1 oligodeoxynucleotides (ODN) resulted in a significant reduction in MMP-1, HGF and c-met. Interestingly, HGF also stimulated ets-1 mRNA in vascular smooth muscle cells, similar to endothelial cells. Of importance, transfection of antisense ets-1 ODN resulted in a significant decrease in vascular endothelial growth factor (VEGF) and HGF expression, whereas HGF stimulated both HGF and VEGF expression. Moreover, in vivo transfection of ets-1 antisense ODN resulted in an inhibition of angiogenesis induced by the HGF gene in a rat ischemic hindlimb model. Conclusions— Here, we demonstrated that HGF stimulated the expression of MMP-1, VEGF, HGF itself, and c-met in human endothelial cells and vascular smooth muscle cells. Upregulation of angiogenesis-related genes was largely dependent on the induction of ets, especially ets-1. These data provide new information about the mechanisms of angiogenesis. |
| Databáze: | OpenAIRE |
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