UBC Theses and Dissertations
The role of red blood cells in wound healing Akbari, Amir
Wound healing is a complex & intricate process that involves the coordinated efforts of an enormous number of unique tissues & cell lineages. Regardless of the cause, defects in this well-orchestrated process often lead to dramatic morbidity and treatments that are among the most costly, from an economic perspective. In an effort to understand the wound healing mechanisms and to establish more effective treatments, the roles of many underlying factors and cell types have been extensively studied. In spite of their ubiquitous presence and involvement in coagulation, thrombosis, and inflammation, the role(s) of red blood cells (RBC) in wound healing remains to be elucidated - RBCs are generally thought of as inert bystanders in wound healing. Recent evidence regarding RBCs novel secondary functions and their ability to actively participate in dynamic biological processes such as inflammation, led us to investigate their role in wound healing. In order to explore RBCs involvement in wound healing, three specific objectives were successfully accomplished in this research project: (1) utilizing Western blot and proteomic analyses the presence of five erythrocytic 14-3-3 isoforms were confirmed, (2) it was established that treatment of dermal fibroblasts with RBC lysate for 24 hours results in significant (p<0.01) upregulation of matrix metalloproteinase (MMP)-1, -2, -3, fibronectin and down regulation of type-I collagen, and (3) utilizing specific inhibitors for three mitogen activated protein kinase (MAPK) pathways, the extracellular regulated protein kinase 1/2 (ERK 1/2) pathway was found to be involved in the RBC mediated upregulation of MMP-1 in dermal fibroblasts. Collectively, this project‟s findings, demonstrate that RBCs are equipped with some form of anti-fibrogenic factor which enables them to actively participate in the dynamic process of ECM modulation, through the activation of ERK 1/2 pathway. Such observations, could potentially pave the way for designing novel treatments for fibrotic disorders such as hypertrophic scars and keloids, which are frequently caused by thermal injuries, surgical incisions and other deep-dermal injuries.
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