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Fister, A. M.

Publications and source records attributed to Fister, A. M..

3 recordsLinked to original sources

Isotonic medium treatment limits burn wound microbial colonization and improves tissue repair

Burn injuries undergo a complex healing process in which progressive spreading of epithelial damage can lead to secondary complications such as wound infection, which is a major driver of mortality among burn patients. We recently reported that burning larval zebrafish triggers dysregulated keratinocyte dynamics compared to mechanical injury. Here, we investigate keratinocyte behavior following burn injury and the subsequent potential for microbial colonization of burn wounds over time. Real-time imaging, coupled with tracking of photoconverted cells, revealed that early keratinocyte motility contributes to the spread of epithelial damage beyond the initial site of burn injury and that increased epithelial damage was associated with wound colonization by the fungal pathogen Candida albicans. Modulating osmotic balance by treating larval zebrafish with isotonic medium limited the spread of epithelial damage and reduced microbial colonization of burn wounds. Using cultured human skin, we found that topical treatment with isotonic solution (saline) similarly prevented the spread of epithelial damage over time. These findings indicate that keratinocyte behavior contribute to burn wound progression in larval zebrafish and link keratinocyte dynamics to microbial colonization of burn wounded tissue.

cell biology↗

Keratinocyte dynamics modulate the spatial organization of redox signaling during sensory neuron regeneration

Epithelial damage leads to early reactive oxygen species (ROS) signaling, which regulates sensory neuron regeneration and tissue repair. How the initial type of tissue injury influences early damage signaling and regenerative growth of sensory axons remains unclear. Previously we reported that thermal injury triggers distinct early tissue responses in larval zebrafish. Here, we found that thermal but not mechanical injury impairs sensory axon regeneration and function. Real-time imaging revealed an immediate tissue response to thermal injury characterized by the rapid Arp2/3-dependent migration of keratinocytes, which was associated with tissue-scale ROS production and sustained sensory axon damage. Isotonic treatment was sufficient to limit keratinocyte movement, spatially restrict ROS production and rescue sensory neuron function. These results suggest that early keratinocyte dynamics regulate the spatial and temporal pattern of long-term signaling in the wound microenvironment during tissue repair.

cell biology↗

MicroRNA-mediated control of developmental lymphangiogenesis

The post-transcriptional mechanisms contributing to molecular regulation of developmental lymphangiogenesis and lymphatic network assembly are not well understood. Here, we use high throughput small RNA sequencing to identify miR-204, a highly conserved miRNA dramatically enriched in lymphatic vs. blood endothelial cells, and we demonstrate that this miRNA plays a critical role during lymphatic development. Suppressing miR-204 leads to loss of lymphatic vessel formation, while overproducing miR-204 in lymphatic vessels accelerates lymphatic vessel formation, suggesting a positive role during developmental lymphangiogenesis. We also identify the NFATC1 transcription factor as a key conserved target for post-transcriptional regulation by miR-204 during lymphangiogenesis. While miR-204 suppression leads to loss of lymphatics, knocking down its target NFATC1 leads to lymphatic hyperplasia, and the loss of lymphatics in miR-204-deficient animals can be rescued by NFATC1 knockdown. Together, our results highlight a miR-204/NFATC1 molecular regulatory axis required for proper lymphatic development.

developmental biology↗