Discipline: Biological Sciences
Subcategory: Cell and Molecular Biology
Mona Chatrizeh - University of California, Los Angeles
Co-Author(s): Aaron M. Ambrus and Hilary A. Coller, University of California, Los Angeles
There is a high rate of diabetic patients that require amputations due to serious infections from having wounds that don’t heal sufficiently. A clearance mechanism is needed at every step of the wound healing to degrade immune cells from the earlier part of the process in order to recruit new cytokines and immune cells. We propose autophagy, a commonly physiological cell clearance mechanism, plays an instrumental role in proper wound healing by being intimately involved in inflammatory response initiation and necrotic cell death. We have found that conditional deletion of autophagy associated gene (ATG7) in a whole body knockout mouse model shows an impairment in wound healing ability when compared to control autophagy proficient littermates. Additionally, we found a similar phenotype when ATG7 was specifically deleted in fibroblast specific protein (FSP) expressing cells, suggesting that autophagy in fibroblasts is important for proper wound healing. Fibroblast functioning is crucial for proper wound healing. Fibroblasts are involved in the wound healing process by first travelling to the site of irritation and then by proliferating to create a de novo tissue. To investigate whether autophagy deficiency in fibroblasts interferes the process of wound healing at a migratory or proliferative level, we have derived mouse embryonic fibroblasts (MEF) from autophagy proficient and deficient mice which will be furthered studied for migration, mobility and proliferation. Furthermore, autophagy deficient cells have previously been noted to have higher levels of cytokines such intereferon-gamma which could represent a mechanism that inhibits wound healing in autophagy-deficient mice. Through migration, proliferation, and cytokine studies, involvement of fibroblasts and autophagy in proper wound healing can be better understood and implemented in medicine.
Funder Acknowledgement(s): National Insitute of Health MARC*USTAR; National Science Foundation Louis Stokes CAMP Scholarship
Faculty Advisor: Hilary Coller, firstname.lastname@example.org
Role: With support and help from my mentors, I was primarily responsible for the experiments and research described.