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E-peptides control bioavailability of IGF-1

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Title: E-peptides control bioavailability of IGF-1
Authors: Hede, MS
Salimova, E
Piszczek, A
Perlas, E
Winn, N
Nastasi, T
Rosenthal, N
Item Type: Journal Article
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.
Issue Date: 10-Dec-2012
Date of Acceptance: 29-Oct-2012
URI: http://hdl.handle.net/10044/1/82142
DOI: 10.1371/journal.pone.0051152
ISSN: 1932-6203
Publisher: Public Library of Science (PLoS)
Start Page: 1
End Page: 11
Journal / Book Title: PLoS One
Volume: 7
Issue: 12
Copyright Statement: © 2012 Hede et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords: Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
GROWTH-FACTOR-I
(IGF)-I E-PEPTIDES
SKELETAL-MUSCLE
EXTRACELLULAR-MATRIX
TRANSGENIC MICE
ACCELERATES MUSCLE
GENE-EXPRESSION
MESSENGER-RNAS
REGENERATION
HYPERTROPHY
Alternative Splicing
Animals
Base Sequence
Biological Availability
Blotting, Northern
DNA Primers
Extracellular Matrix
HEK293 Cells
Humans
Immunohistochemistry
Insulin-Like Growth Factor I
Mice
Mice, Transgenic
Peptides
Protein Binding
Extracellular Matrix
Animals
Mice, Transgenic
Humans
Mice
Peptides
Insulin-Like Growth Factor I
DNA Primers
Blotting, Northern
Immunohistochemistry
Alternative Splicing
Base Sequence
Protein Binding
Biological Availability
HEK293 Cells
Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
GROWTH-FACTOR-I
(IGF)-I E-PEPTIDES
SKELETAL-MUSCLE
EXTRACELLULAR-MATRIX
TRANSGENIC MICE
ACCELERATES MUSCLE
GENE-EXPRESSION
MESSENGER-RNAS
REGENERATION
HYPERTROPHY
General Science & Technology
Publication Status: Published
Article Number: ARTN e51152
Online Publication Date: 2012-12-10
Appears in Collections:National Heart and Lung Institute



This item is licensed under a Creative Commons License Creative Commons