The long-term objective of this project is to elucidate the mechanisms which initiate and control wound repair. We have isolated a growth factor, Mesodermal Growth Factor (MGF) and its components, MGF-I and MGF-II, which potently stimulate cell growth. MGF is one of the few growth factors found to act both in vitro and in vivo. MGF acts as a mitogen on corneal stromal fibroblasts in tissue culture; accelerates wound healing in rat, rabbit and human endothelium in organ culture; accelerates the normal healing process with reduced scarring in rabbit and monkey corneal stroma in vivo; and improves endothelial repair in cat cornea in vivo. The studies proposed will concentrate on further purification of MGF-I and MGF-II. To characterize MGF components, new chromatographic techniques and tissue culture bioassays for DNA synthesis and mitogenicity will be employed. Antibodies to MGF-I and MGF-II will be refined and used to improve the purification process, and to help identify these MGF components in other factors and tissues. An affiliated laboratory will provide amino acid composition and N-terminal sequences of MGF components. Although this project is in its twenty-fifth year, a new Principal Investigator has redirected priorities. As this proposal is a resubmission, a discussion of the reviewers' critique of the previous application is included (see pages 7-8). The restated Specific Aims of this grant proposal address the necessity of refining the biochemical description of MGF components. Responses to each of the reviewers' concerns are outlined and annotated throughout the text of the proposal.
