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Title: INSULIN-LIKE GROWTH FACTOR-I: A TRAFFIC CONTROL DEVICE ON THE ROAD TO TISSUE RECOVERY

Author
item Elsasser, Theodore

Submitted to: American Journal of Physiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/23/2003
Publication Date: 10/1/2003
Citation: Elsasser, T.H. 2003. Insulin-like growth factor-I: A traffic control device on the road to tissue recovery. American Journal of Physiology. 285:R722-R723.

Interpretive Summary: For years following its identification as the peptide that modulates the anabolic activities of growth hormone, insulin-like growth factor-1 (IGF-1) has largely been thought of in a nutrition and growth regulator. We now see that the role of IGF-1 in the body is significantly more sophisticated than originally thought, in particular as regards its interaction with the immune system through a systematized influence of several signal transduction pathways that accelerate or retard tissue growth as the scenario dictates. The feature discussed herein is that through the use of a technique called gene transfer, a specific delivery of the IGF-1 gene can be delivered to a tissue region and only that region will be affected by the subsequent manufacture and production of IGF-1 protein. To accomplish this, the active part of the IGF-1 gene is biochemically placed inside another set of genes that will allow the IGF-1 gene to be activated inside the body. The gene set is mixed into a fatty matrix and injected by needle into a specific site. In this manner, the actions of IGF-1 are present only locally and do not interfere with other body functions. Therefore wound healing can be hastened locally improving the health of the patient.

Technical Abstract: This review article serves to create a logic path originating with generalizations regarding insulin-like growth factor-1 (IGF-1) as a system wide growth factor affecting protein and energy use on a whole body basis and ending with specific novel roles for IGF-1 as a multifunctional regulator of apoptosis and tissue repair. The review serves as an invited 'Editorial Focus' for the American Journal of Physiology highlighting a series of papers written by Jeschke et al., that describe the utility of site-directed, liposome-mediated IGF-1 gene transfer as a therapeutic advance to speed tissue healing and wound repair in animals. In the process of reviewing relevant literature, this paper demonstrates how the biochemical attributes of IGF-1 can be temporally up- and down-regulated in controlling the proinflammatory mediator nuclear factor kappa-B (NF-'B).