Profiling and metaanalysis of epidermal keratinocytes responses to epidermal growth factor

Abstract

BackgroundOne challenge of systems biology is the integration of new data into the preexisting, and then re-interpretation of the integrated data. Here we use readily available metaanalysis computational methods to integrate new data on the transcriptomic effects of EGF in primary human epidermal keratinocytes with preexisting transcriptomics data in keratinocytes and in EGF-treated non-epidermal cell types.ResultsWe find that EGF promotes keratinocyte proliferation, attachment and motility and, surprisingly, induces DUSPs that attenuate the EGF signal. Our metaanalysis identified overlapping effects of EGF with those of IL-1 and IFNγ, activators of keratinocyte in inflammation and wound healing. We also identified the genes and pathways suppressed by EGF but induced by agents promoting epidermal differentiation. Metaanalysis comparison with the EGF effects in other cell types identified extensive similarities between responses in keratinocytes and in other epithelial cell types, but specific differences with the EGF effects in endothelial cells, and in transformed, oncogenic epithelial cell lines.ConclusionsThis work defines the specific transcriptional effects of EGF on human epidermal keratinocytes. Our approach can serve as a suitable paradigm for integration of new omics data into preexisting databases and re-analysis of the integrated data sets.

Asymmetric Migration of Human Keratinocytes under Mechanical Stretch and Cocultured Fibroblasts in a Wound Repair Model

“…Thus, it is reasonably speculated that HaCaT cells simply tends to move away from HF cells, which is mainly due to EGF secreted by HF cells to create an EGF gradient, hence the directionality of HaCaT migration. These results imply a typical case of EGF chemotaxis or possibly a differential migration speed due to different EGF concentrations, which is also consistent with keratinocyte responses to EGF concentrations and gradient in the literatures [47]–[49]. Further studies demonstrated that mechanical stretch subjected to fibroblasts fostered keratinocyte asymmetric migration by increasing EGF secretion (Figs.…”

A cellular perspective of bias at G protein‐coupled receptors

“…Such approaches show that GPCR signaling can activate the transcription of hundreds of genes 39,62–64 . As a point of comparison, activation of RTKs can induce changes to the transcription of ~1,000 genes 65–67 . Christensen et al compared how the full agonist AngII and the biased agonist SII changed transcription downstream of AT1R 62 .…”

Low EGF in myeloablative allotransplantation: association with severe acute GvHD in BMT CTN 0402

“…Epidermal growth factor (EGF) is a peptide growth factor central to restoration of epithelial and mucosal integrity after injury 1–3 . Receptors for EGF are located on keratinocytes in the basal layer of the epidermis 4 and basolateral surfaces of intestinal epithelial cells, particularly in crypts 5 , suggesting that EGF signaling may be critical for tissue repair after damage in these acute graft-versus-host disease (aGVHD) target organs.…”