The skin is the largest organ of the body and its primary function is to serve as a protective barrier against the external environment. Injury to the skin requires prompt resurfacing in order to re-establish this protective function. Healing of a skin wound is a highly complex, dynamic process involving contraction, cell proliferation, cell migration, production of an extracellular matrix, and remodeling. It is now appreciated that a number of growth substances participate in the healing process to coordinate the interaction between the cells involved. We have discovered that an endogenous opioid system, comprised of [Met5]-enkephalin (termed opioid growth factor, OGF) and its receptor (OGFr), modulates homeostasis and re-epithelialization in human and mouse skin. This native opioid peptide is autocrine- and possibley paracrine-produced and interacts with its receptor to tonically inhibit DNA synthesis, and retard cellular proliferation in a non-cytotoxic and reversible fashion. In this grant we propose to test the hypothesis that OGF-OGFr interactions participate in the healing of a full-thickness skin wound and that the repair process can be modulated by pharmacologically manipulating OGFr. Experiments are designed to test this hypothesis by examining the consequences of cellular and molecular perturbation of the peptide, and of the receptor, in order to delineate their individual contributions to skin repair, with a focus on cellular proliferation, migration, and differentiation. The planned studies are part of a long-range program directed towards understanding the mechanisms involved in maintenance and repair of the epidermis. Furthermore, if our hypothesis is proven, manipulation of the endogenous OGF system represents a potential chemotherapeutic modality for the management of wounds.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Small Research Grants (R03)
Project #
5R03AR048666-02
Application #
6752880
Study Section
Special Emphasis Panel (ZAR1-RJB-A (O3))
Program Officer
Moshell, Alan N
Project Start
2003-06-01
Project End
2006-05-31
Budget Start
2004-06-01
Budget End
2005-05-31
Support Year
2
Fiscal Year
2004
Total Cost
$74,850
Indirect Cost
Name
Pennsylvania State University
Department
Veterinary Sciences
Type
Schools of Medicine
DUNS #
129348186
City
Hershey
State
PA
Country
United States
Zip Code
17033
Sassani, Joseph W; Mc Laughlin, Patricia J; Zagon, Ian S (2016) The Yin and Yang of the Opioid Growth Regulatory System: Focus on Diabetes-The Lorenz E. Zimmerman Tribute Lecture. J Diabetes Res 2016:9703729