GSE134113
AP-1 transcriptional activity drives micrograft-mediated cell migration and promotes the matrix remodeling machinery
Impaired wound healing and tissue regeneration have severe consequences on the patient's life quality. Micrograft therapies are emerging as promising and affordable alternatives to improve skin regeneration by enhancing the endogenous wound repair processes. However, the molecular mechanisms underpinning the beneficial effects of the micrograft treatments remain largely unknown. 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 micrograft-treated mouse adult fibroblasts and in the human keratinocyte (HaCaT) cell model. Accordingly, we show that increased micrograft-dependent in vitro cell migration and matrix metalloprotease activity is abolished upon inhibition of AP-1. Furthermore, micrograft treatment leads to increased expression and post-translational phosphorylation of Fra-1 and c-Jun, resulting in the upregulation of wound healing associated genes mainly involved in the regulation of cell migration. Collectively, our work provides insights into the molecular mechanisms behind micrograft treatments, which might contribute to future advances in wound repair therapies. Overall design: A total of 3 samples (3 biological replicates) have been used to analyse transcriptome changes in wounded murine primary fibroblasts upon 5h of Micrograft (MG) treatment in association with MEK inhibitor PD0325901 (ERK signalling pathway inhibition).