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Upon injury, several transcription factors are triggered by the damaged tissue. During wound healing, sequential cellular processes are actively coordinated by waves of growth factors and cytokines. Their activation is tightly regulated by signaling cascades that translate the input of intrinsic and extrinsic factors into a transcriptional cellular response to such cellular changes. The process of wound healing emerges as a result of a complex interplay between transcription factors that regulate essential transcriptional networks.
Activator protein skin#
Therefore, optimal tissue regeneration and proper wound management are required to maintain skin integrity. Traumatic injuries and impaired wound healing greatly affect the quality of life of patients and eventually contribute to mortality. The skin is the largest organ of the human body providing protection, immune defense, and sensation. Collectively, our work provides insights into the molecular mechanisms behind the cell-free micrograft treatment, which might contribute to future advances in wound repair therapies. Furthermore, soluble micrograft treatment leads to increased expression and posttranslational phosphorylation of Fra-1 and c-Jun, resulting in the upregulation of wound healing-associated genes mainly involved in the regulation of cell migration. Accordingly, we show that increased micrograft-dependent in vitro cell migration and matrix metalloprotease activity is abolished upon inhibition of AP-1. In this study, we identified the active protein-1 (AP-1) member Fos-related antigen-1 (Fra-1) to play a central role in the extracellular signal-regulated kinase- (ERK-) mediated enhanced cell migratory capacity of soluble micrograft-treated mouse adult fibroblasts and in the human keratinocyte cell model. However, the molecular mechanisms underpinning the beneficial effects of the micrograft treatments remain largely unknown.
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Micrograft therapies are emerging as promising and affordable alternatives to improve skin regeneration by enhancing the endogenous wound repair processes. Impaired wound healing and tissue regeneration have severe consequences on the patient’s quality of life.