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Engineering insulin‐like growth factor‐1 for local delivery
| Content Provider | Scilit |
|---|---|
| Author | Tokunou, Tomotake Miller, Rachel Patwari, Parth Davis, Michael E. Segers, Vincent F. M. Grodzinsky, Alan J. Lee, Richard T. |
| Copyright Year | 2008 |
| Description | Journal: The FASEB Journal Insulin-like growth factor-1 (IGF-1) is a small protein that promotes cell survival and growth, often acting over long distances. Although for decades IGF-1 has been considered to have therapeutic potential, systemic side effects of IGF-1 are significant, and local delivery of IGF-1 for tissue repair has been a long-standing challenge. In this study, we designed and purified a novel protein, heparin-binding IGF-1 (Xp-HB-IGF-1), which is a fusion protein of native IGF-1 with the heparin-binding domain of heparin-binding epidermal growth factor-like growth factor. Xp-HB-IGF-1 bound selectively to heparin as well as the cell surfaces of 3T3 fibroblasts, neonatal cardiac myocytes and differentiating ES cells. Xp-HB-IGF-1 activated the IGF-1 receptor and Akt with identical kinetics and dose response, indicating no compromise of biological activity due to the heparin-binding domain. Because cartilage is a proteoglycan-rich environment and IGF-1 is a known stimulus for chondrocyte biosynthesis, we then studied the effectiveness of Xp-HB-IGF-1 in cartilage. Xp-HB-IGF-1 was selectively retained by cartilage explants and led to sustained chondrocyte proteoglycan biosynthesis compared to IGF-1. These data show that the strategy of engineering a "long-distance" growth factor like IGF-1 for local delivery may be useful for tissue repair and minimizing systemic effects. |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2754573/pdf |
| Ending Page | 1893 |
| Page Count | 8 |
| Starting Page | 1886 |
| ISSN | 08926638 |
| e-ISSN | 15306860 |
| DOI | 10.1096/fj.07-100925 |
| Journal | The FASEB Journal |
| Issue Number | 6 |
| Volume Number | 22 |
| Language | English |
| Publisher | Wiley-Blackwell |
| Publisher Date | 2008-01-29 |
| Access Restriction | Open |
| Subject Keyword | Journal: The FASEB Journal Biotechnology and Microbiology Heparin Binding Domain |
| Content Type | Text |
| Resource Type | Article |
| Subject | Genetics Medicine Molecular Biology Biochemistry Biotechnology |