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Biology subjects

DiPietro, L. A.

Publications and source records attributed to DiPietro, L. A..

4 recordsLinked to original sources

A role for CREB5 in skin wound healing

Compared with skin wounds, oral mucosal wounds heal more quickly, with minimal scarring, faster re-epithelialization, and reduced inflammation. One differentiating factor may be the differential transcription factor-associated gene networks involved in tissue regeneration. One such transcription factor, BATF3, was recently shown by us to promote wound-healing responses in vitro and in vivo. Our prior analyses also suggest that CREB5 is a differentially regulated transcription factor in oral wounds and may be involved in early wound-healing gene expression programs. CREB5 expression was induced in immortalized skin keratinocytes (HaCaT) to examine its effect on in vitro wound healing relative to immortalized gingival keratinocytes (TIGK). CREB5 overexpression let to differential expression of predicted downstream genes and improved skin keratinocyte migration in vitro. This work suggests that examining transcription factors and gene networks that regulate wound-healing responses in the oral mucosa may lead to the discovery of novel targets to improve skin wound healing.

cell biology↗

A role for ETV1 and endothelial cell-derived extracellular vesicle microRNAs in priming fibroblast response to vesicle-bound FGF2

Communication between various cell types following wounding is paramount for proper healing and regeneration of injured tissue. Endothelial cells and fibroblasts are critical cellular players involved in cutaneous wound repair, yet their communication mechanisms are not well understood. It has previously been shown that extracellular vesicles derived from endothelial cells (ECEVs) induce dermal fibroblasts to express a gene signature correlated with FGF2-mediated cancer associated fibroblast (CAF) activation, under the control of transcription factor ETV1. In this report, we utilize loss-of-function studies to define the mechanistic role of ETV1 in conferring this ECEV-induced transcriptomic shift and functional change in fibroblasts. Additionally, we identify highly expressed ECEV microRNAs and examine their potential contribution to the ECEV mechanism through downstream gene modulation. In summary, we describe a plausible mechanism by which both ETV1 and top ECEV microRNAs promote a genotypic and phenotypic shift in dermal fibroblasts that have taken up ECEVs.

cell biology↗

Transcriptional changes in human palate and skin healing

Most human tissue injuries lead to the formation of a fibrous scar and result in the loss of functional tissue. One adult tissue that exhibits a more regenerative response to injury with minimal scarring is the oral mucosa. We generated a microarray gene expression dataset to examine the response to injury from human palate and skin excisional biopsies spanning the first seven days after wounding. Differential expression analyses were performed in each tissue to identify genes overexpressed or underexpressed over time compared to baseline unwounded tissue. To attribute biological processes of interest to these gene expression changes, gene set enrichment analysis was used to identify core gene sets that are enriched over the time-course of the wound healing process with respect to unwounded tissue. This analysis identified gene sets uniquely enriched in either palate or skin wounds and gene sets that are enriched in both tissues in at least one time point after injury. Finally, a cell-deconvolution analysis was performed to better understand the cell type distribution in these tissues and how it changes over the time course of wound healing. This work provides a source of human wound gene expression data that includes two tissue types with distinct regenerative and scarring phenotypes.

cell biology↗

The healing potential of wild type and recombinant S100A8 to attenuate skin wound inflammation

BackgroundWounds represent a major health burden in our society and poorly healing wounds are a significant clinical problem worldwide, During the acute inflammatory, neutrophils which are normal wound scavengers seems to create additional tissue destruction and promote scar formation. This project examined the utility of using pluronic gel to deliver ala42S100A8, a peptide that repels neutrophils, to wounds, allowing more regenerative repair. MethodExcisional wound models on female BALB/c mice were made and 4 treatments including pluronic gel only group, Wild type S100A8 (1, 2, and 4g) with Pluronic gel, and ala42S100A8 (1, 2, and 4g) with Pluronic gel were applied to the wounds. Wounds were harvested at day 1 and day 3. Myeloperoxidase (MPO) protein level was examined using an ELISA kit and cytokine protein expression of CXCL1 (GRO-1), CXCL2 (MIP-2). IL-6, and TNF- was determined using a multiplex ELISA kit. ResultsMPO level in Pluronic gel treated wounds at day 1 was significantly higher than that in control, suggesting that the Pluronic gel itself causes increased inflammation in wounds, while treatment with 1g of s100A8 or 1 and 4g of ala42S100A8 seemed to decrease MPO at day 1 compared to the Pluronic gel treated wounds. Treatment with 1g of s100A8 also led to a decrease IL-6 and TNF- production at day 1 when compared to the Pluronic gel group, although no statistical difference was observed ConclusionsOur findings strongly suggest that wound inflammation is reduced by treatment with 1ug of S100A8. As such, this study provides proof-of-principal for further investigations of S100A8/ala42S100A8 as a wound therapeutic. Additional studies with lower doses and increased sample size, along with the use of alternative delivery systems, will provide important information about the utility of this approach.

immunology↗