Pleiotrophin-mediated improvement of collagen fibrous structure leads to dermal regeneration.

Summary: Abstract Body: Pleiotrophin is a secreted growth factor expressed in various tissues, including the nervous system, and has been reported to be involved in development and regeneration. It is also expressed in the skin and is expected to influence regeneration, although the findings remain limited. In this study, the effects of pleiotrophin on dermal component cells were examined from the perspective of tissue regeneration. The effects of pleiotrophin added to three cell types considered to contribute to dermal regeneration were evaluated, and the results were as follows: (1) Fibroblasts: Pleiotrophin enhanced the expression of genes involved in the organization and degradation of the extracellular matrix, as well as secreted factors such as growth factors. It is possible that pleiotrophin not only promotes the remodeling of fibrous structure, but also affects the surrounding cells via secreted factors. (2) Vascular endothelial cells: Pleiotrophin enhanced angiogenesis, which may promote the exchange of nutrients and other substances necessary for dermal regeneration. (3) Macrophages: Phagocytosis was enhanced by pleiotrophin. By removing unnecessary cells and substances from the tissues, it may contribute to preparing the tissue environment for dermal regeneration. Next, the effects of pleiotrophin on dermal collagen fibrous structure were evaluated using fresh skin fragments that were just excised from the living body and in which the responsiveness of cells was maintained. When the skin fragments were cultured in the presence of pleiotrophin for 7 days, not only was there an improvement in fiber density, but also a decrease in contracted fiber structure and the neogenesis of fine fibers, indicating an improvement in dermal structure. In summary, our findings suggest that pleiotrophin may play a key role in improving the structural deterioration of dermal collagen associated with aging, by affecting dermal component cells and promoting dermal regeneration. Satomi Kiuchi¹, Ami Seino¹, Hiroko Ochiai², Koji Mizukoshi¹ 1. POLA Chemical Industries, Inc., Yokohama, Japan. 2. Department of Plastic and Reconstructive Surgery, National Hospital Organization Tokyo Medical Center, Tokyo, Japan. Cell Communication Networks and Stromal Biology