Potential Mechnanisms for Pentadecapeptide PL 14736 to Promote the Wound Healing in Diabetes

As the diet and living habits of people in Taiwan become westernized, the number of diabetic patients in Taiwan has been kept increasing. Diabetes significantly increases the risk for many other diseases such as cardiovascular and kidney diseases. Another example is the impaired wound healing in diabetic patients and some severe cases may result in the limb amputation. Currently, only becaplermin (recombinant human platelet-derived growth factor homodimer of B chains, PDGF-BB, Regranex,), a very expensive standard therapy, is used to improve the healing of diabetic foot. Nowadays, no other alternative drug with same efficacy is available. The discovery of pepntadecapeptide PL 14736 from gastric juice was first identified in 1993 which was later found to efficiently improve the healing of various tissues or organ. However, very few studies have been performed to investigate the detailed molecular mechanisms. The present study is aimed to further understand the potential mechanisms underlying the beneficial effects of PL 146736 on improving the healing of diabetic wounds. The study will first be focused on investigating the effects of PL 14736 on angiognesis and the fibroblast functions including proliferation and migration. As we know that the synthesis of pentadecapeptide is relatively simple and small dose ranged between ng- μg/ml is already effective. The experimental results of this study will lead and shed light on the understanding of PL 14736 efficacy and explore the future application of PL 14736 therapy to many other different diseases. This study will be carried out in three years: The first year--to investigate the effects of PL 14736 on the in vivo and in vitro angiogenesis and the gene expressions of pro-angiogenic factors; The second year--to investigate the effects of PL 14736 on improving the wound healing in diabetic mice and the function of endothelial progenitor cells in the blood; The third year--to investigate the effects of PL 14736 on the proliferation and migration of fibroblasts both in vivo and in vitro, and the expressions of growth-related genes.

Project ID:PC9808-0537
External Project ID:NSC98-2320-B182-035-MY3