E-peptides control bioavailability of IGF-1.
Insulin-like growth factor 1 (IGF-1) is a potent cytoprotective growth factor that has attracted considerable attention as a promising therapeutic agent. Transgenic over-expression of IGF-1 propeptides facilitates protection and repair in a broad range of tissues, although transgenic mice over-expre...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3519493?pdf=render |
| _version_ | 1811268915266846720 |
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| author | Marianne Smedegaard Hede Ekaterina Salimova Agnieszka Piszczek Emarald Perlas Nadine Winn Tommaso Nastasi Nadia Rosenthal |
| author_facet | Marianne Smedegaard Hede Ekaterina Salimova Agnieszka Piszczek Emarald Perlas Nadine Winn Tommaso Nastasi Nadia Rosenthal |
| author_sort | Marianne Smedegaard Hede |
| collection | DOAJ |
| description | Insulin-like growth factor 1 (IGF-1) is a potent cytoprotective growth factor that has attracted considerable attention as a promising therapeutic agent. Transgenic over-expression of IGF-1 propeptides facilitates protection and repair in a broad range of tissues, although transgenic mice over-expressing IGF-1 propeptides display little or no increase in IGF-1 serum levels, even with high levels of transgene expression. IGF-1 propeptides are encoded by multiple alternatively spliced transcripts including C-terminal extension (E) peptides, which are highly positively charged. In the present study, we use decellularized mouse tissue to show that the E-peptides facilitate in vitro binding of murine IGF-1 to the extracellular matrix (ECM) with varying affinities. This property is independent of IGF-1, since proteins consisting of the E-peptides fused to relaxin, a related member of the insulin superfamily, bound equally avidly to decellularized ECM. Thus, the E-peptides control IGF-1 bioavailability by preventing systemic circulation, offering a potentially powerful way to tether IGF-1 and other therapeutic proteins to the site of synthesis and/or administration. |
| first_indexed | 2024-04-12T21:31:17Z |
| format | Article |
| id | doaj.art-8b7a2fe0351b4a6895f1aa045c95f201 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T21:31:17Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-8b7a2fe0351b4a6895f1aa045c95f2012022-12-22T03:16:01ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-01712e5115210.1371/journal.pone.0051152E-peptides control bioavailability of IGF-1.Marianne Smedegaard HedeEkaterina SalimovaAgnieszka PiszczekEmarald PerlasNadine WinnTommaso NastasiNadia RosenthalInsulin-like growth factor 1 (IGF-1) is a potent cytoprotective growth factor that has attracted considerable attention as a promising therapeutic agent. Transgenic over-expression of IGF-1 propeptides facilitates protection and repair in a broad range of tissues, although transgenic mice over-expressing IGF-1 propeptides display little or no increase in IGF-1 serum levels, even with high levels of transgene expression. IGF-1 propeptides are encoded by multiple alternatively spliced transcripts including C-terminal extension (E) peptides, which are highly positively charged. In the present study, we use decellularized mouse tissue to show that the E-peptides facilitate in vitro binding of murine IGF-1 to the extracellular matrix (ECM) with varying affinities. This property is independent of IGF-1, since proteins consisting of the E-peptides fused to relaxin, a related member of the insulin superfamily, bound equally avidly to decellularized ECM. Thus, the E-peptides control IGF-1 bioavailability by preventing systemic circulation, offering a potentially powerful way to tether IGF-1 and other therapeutic proteins to the site of synthesis and/or administration.http://europepmc.org/articles/PMC3519493?pdf=render |
| spellingShingle | Marianne Smedegaard Hede Ekaterina Salimova Agnieszka Piszczek Emarald Perlas Nadine Winn Tommaso Nastasi Nadia Rosenthal E-peptides control bioavailability of IGF-1. PLoS ONE |
| title | E-peptides control bioavailability of IGF-1. |
| title_full | E-peptides control bioavailability of IGF-1. |
| title_fullStr | E-peptides control bioavailability of IGF-1. |
| title_full_unstemmed | E-peptides control bioavailability of IGF-1. |
| title_short | E-peptides control bioavailability of IGF-1. |
| title_sort | e peptides control bioavailability of igf 1 |
| url | http://europepmc.org/articles/PMC3519493?pdf=render |
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