E-peptides control bioavailability of IGF-1

Marianne Hede, Ekaterina Salimova, Agnieszka Piszczek, Emarald Perlas, Nadine Winn, Tommaso Nastasi, Nadia Alicia Rosenthal

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Abstract

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.
Original languageEnglish
Article numbere51152
Number of pages11
JournalPLoS ONE
Volume7
Issue number12
DOIs
Publication statusPublished - 2012

Cite this

Hede, M., Salimova, E., Piszczek, A., Perlas, E., Winn, N., Nastasi, T., & Rosenthal, N. A. (2012). E-peptides control bioavailability of IGF-1. PLoS ONE, 7(12), [e51152]. https://doi.org/10.1371/journal.pone.0051152